Final program and abstracts booklet in Acrobat file format

Montréal
35 e Symposium international
Groupe de Recherche sur le Système Nerveux Central
May 6-7 mai 2013
DROGUES D’ABUS
ET TROUBLES PSYCHIATRIQUES Aspects neurobiologiques et cliniques
DRUGS OF ABUSE
AND PSYCHIATRIC DISEASES Neurobiological and Clinical Aspects
Programme et résumés
Program and abstracts
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1-1-5-15 / 10-07
35e Symposium international
du Groupe de recherche sur le système nerveux central
Montréal, May 6-7 mai 2013
DROGUES D'ABUS ET TROUBLES PSYCHIATRIQUES:
ASPECTS NEUROBIOLOGIQUES ET CLINIQUES
DRUGS OF ABUSES AND PSYCHIATRIC DISEASES:
NEUROBIOLOGICAL AND CLINICAL ASPECTS
Programme / Program
Organisateurs / Organizers
Louis-Éric Trudeau
Daniel Lévesque
Pierre-Paul Rompré
Anne-Noël Samaha
Emmanuel Stip
PROGRAMME
PROGRAM
Lundi, 6 mai 2013
A.M.
8h30 - 8h45
Monday, May 6, 2013
Mot de bienvenue / Welcome address
Trevor Drew, directeur du GRSNC
Daniel Bourbonnais, vice-doyen, Faculté de médecine, Direction
Introduction
Louis-Éric Trudeau, organisateur du symposium
SESSION 1
CANNABIS: RÉCOMPENSE ET PSYCHOSE /
CANNABIS: REWARD AND PSYCHOSIS
Modérateur / Chairperson: Louis-Éric Trudeau, Université de Montréal
A.M.
8h45 - 9h30
Carl Lupica
Electrophysiology Research Section, NIH\NIDA-IRP,
Triad Technology Center, Baltimore, MD, U.S.A.
Endogenous cannabinoids released from midbrain dopamine neurons modify
synaptic processes.
9h30 - 10h15
Joseph F. Cheer
Department of Anatomy and Neurobiology, Department of Psychiatry,
University Maryland School of Medicine, Baltimore, MD, U.S.A.
Endocannabinoid control of dopaminergic signaling in conditioned punishment and
its successful avoidance.
10h15 - 10h30 Pause / Break
10h30 - 11h15 Daniela Parolaro
Department of Theoretical and Apllied Sciences, Biomedical Reasearch Division,
Center of Neuroscience, University of Insubria, Busto Arsizio, VA, ITALY
Cannabis abuse in adolescence and the risk of psychosis: preclinical evidences.
11h15 - 12h00 Colm O'Tuathaigh
School of Medicine,
University College Cork, Cork, IRELAND
Genetic dissection of the psychotomimetic effects of cannabinoid exposure in mice.
12h00 - 13h00 Repas / Lunch
13h00 - 13h30 Session d'affiches / Poster Session
Page 3
PROGRAMME
PROGRAM
Lundi, 6 mai 2013
Monday, May 6, 2013
SESSION 1 (SUITE / CONTINUED)
CANNABIS: RÉCOMPENSE ET PSYCHOSE /
CANNABIS: REWARD AND PSYCHOSIS
Modérateur / Chairperson: Emmanuel Stip, Université de Montréal
13h30 - 14h15 Matthijs G. Bossong
Department of Psychosis Studies, Institute of Psychiatry,
King's College London, London, UNITED KINGDOM
Acute effects of cannabis on human brain functions relevant for psychosis.
14h15 - 15h00 Anissa Abi-Dargham
Department of Psychiatry,
Columbia University & New York State Psychiatric Institute, New York, NY, U.S.A.
Imaging dopamine function in cannabis users.
15h00 - 15h15 Pause / Break
15h15 - 16h00 Sagnik Bhattacharyya
Department of Psychosis Studies, Institute of Psychiatry,
King's College London, London, UNITED KINGDOM
Complexities in the cannabis and psychosis story.
16h00 - 17h00 Conférence plénière / Plenary lecture (introduction par / by Dr. Daniel Lévesque)
Anja C. Huizink
Department of Developmental Psychology, Faculty of Psychology and Education (FPP),
VU University Amsterdam, Amsterdam, THE NETHERLANDS
An overview of studies on prenatal cannabis exposure and infant outcomes.
17h00 - 18h00 Session d'affiches / Poster session
18h30
Page 4
Cocktail et/and Banquet
Agora Morris et Rosalind Goodman
Pavillon Jean-Coutu
Campus de l'Université de Montréal
2940, chemin de Polytechnique
PROGRAMME
PROGRAM
Mardi, 7 mai 2013
Tuesday, May 7, 2013
SESSION 2
PSYCHOSTIMULANTS ET NICOTINE:
RÉCOMPENSE, PLASTICITÉ SYNAPTIQUE ET TROUBLES PSYCHIATRIQUES /
PSYCHOSTIMULANTS AND NICOTINE:
REWARD, SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Modérateur / Chairperson: Pierre-Paul Rompré, Université de Montréal
A.M.
8h45 - 9h30
Antonello Bonci
National Institute on Drug Abuse,
Johns Hopkins, Baltimore, MD, U.S.A.
New tricks form an old dog: synaptic plasticity and substance abuse.
9h30 - 10h15
Anne-Noël Samaha
Département de pharmacologie, Faculté de médecine,
Université de Montréal, Montréal, QC, CANADA
Chronic antipsychotic treatment enhances reward function in the rat.
10h15 - 10h30 Pause / Break
10h30 - 11h15 Bernard Le Foll
Translational Addiction Research Laboratory, Center for Addiction and Mental Health,
University of Toronto, Toronto, ON, CANADA
A translational approach to discover new treatments for nicotine addiction.
11h15 - 11h45 Session d'affiches / Poster session
11h45 - 12h45 Repas / Lunch
Page 5
PROGRAMME
PROGRAM
Mardi, 7 mai 2013
Tuesday, May 7, 2013
SESSION 2 (SUITE / CONTINUED)
PSYCHOSTIMULANTS ET NICOTINE:
RÉCOMPENSE, PLASTICITÉ SYNAPTIQUE ET TROUBLES PSYCHIATRIQUES /
PSYCHOSTIMULANTS AND NICOTINE:
REWARD, SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Modératrice / Chairperson: Anne-Noël Samaha, Université de Montréal
P.M.
12h45 - 13h30 Tony P. George
Department of Psychiatry, University of Toronto,
Center for Addiction and Mental Health, Toronto, ON, CANADA
The effects of tobacco smoking and nicotine on neurocognitive endophenotypes in
schizophrenia: therapeutic implications.
13h30 - 14h15 Isabelle Boileau
Center for Addiction and Mental Health,
University of Toronto, Toronto, ON, CANADA
Does the D3 dopamine receptor play a role in stimulant addiction?
14h15 - 15h00 Timothy Edwin Wilens
Pediatric Psychopharmacology Research Unit,
Massachusetts General Hospital, Cambridge, MA, U.S.A.
When psychostimulants, nicotine, and ADHD collide.
15h00 - 15h15 Pause / Break
15h15 - 16h00 Scott H. Kollins
Department of Psychiatry and Behavioral Sciences,
Duke University Medical Center, Durham, NC, U.S.A.
ADHD and altered dopamine neurotransmission: Implications for psychostimulant
and nicotine addiction.
16h00 - 17h00 Forum / Debate
Modérateurs / Chairpersons:
Patricia Conrod, Anne-Noël Samaha et / and Emmanuel Stip
Conférenciers / Speakers:
Sagnik Bhattacharyya, Antonello Bonci, Bernard Le Foll et / and Joseph F. Cheer
How to better translate basic neurobiological research into clinically relevant
approaches to treat drug abuse co-morbidity in psychiatric disorders.
17h00 - 17h15 Mot de clôture / Closing remarks
Page 6
35e Symposium international
du Groupe de recherche sur le système nerveux central
Montréal, May 6-7 mai 2013
DROGUES D'ABUS ET TROUBLES PSYCHIATRIQUES:
ASPECTS NEUROBIOLOGIQUES ET CLINIQUES
DRUGS OF ABUSES AND PSYCHIATRIC DISEASES:
NEUROBIOLOGICAL AND CLINICAL ASPECTS
Résumés / Abstracts
Index des résumés en page 29
Index of abstracts on page 29
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
1
L'INTERNALISATION CONTRIBUE À LA DÉSENSIBILISATION DE L'INHIBITION DE
L'AMPC PAR LES LIGANDS DU RÉCEPTEUR OPIOÏDE DELTA
H. BAGHERI 1, 2 , D. ROBERTSON 1, 2 , G. PINEYRO 1, 2
1
Département de pharmacologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada , 2Centre de recherche du CHU Sainte-Justine,
Montréal, QC, Canada .
Les opiacés sont des analgésiques très efficaces pour le traitement des douleurs sévères, mais leur administration prolongé
peut induire de la tolérance à l'analgésie. Au niveau moléculaire, la tolérance aux opiacés serait associée à la désensibilisation
du récepteur et à la perte de sa capacité à signaliser. Étant donné que l'effet thérapeutique des opiacés dépend des signaux
induits par chaque ligand, nous pensons que l'endocytose est un des facteurs déterminants de la tolérance analgésique. Dans
ce contexte, nous pouvons émettre l'hypothèse que la capacité d'un agoniste à induire l'internalisation du récepteur détermine
sa durée de signalisation, ainsi que la tolérance à l'analgésie. Objectif : Pour tester notre hypothèse, nous avons caractérisé
différents opiacés en fonction de leur capacité à inhiber la production d'AMPc et à induire l'internalisation du récepteur dans
les cellules HEK 293. Méthodologie : Le biosenseur EPAC exprimé dans les cellules HEK 293 nous a permis de mesurer la
capacité des différents ligands à moduler l'AMPc par des courbes doses-réponses et d'évaluer la durée de signalisation par des
expériences cinétiques. Résultats : Dans les cellules HEK 293, l'ordre maximal d'internalisation est DPDPE = Deltorphine B
= SNC-80 = Met-Enkephaline>>>mcpTIPP>SB235863=morphine. En ce qui concerne la capacité des agonistes à inhiber la
voie cyclase les opiacés ne different pas dans leur capacité à moduler la production d'AMPc, mais les agonistes inhibent
l'AMPc avec différentes puissances. La durée d'inhibition de l'AMPc est plus courte pour la met-enkephaline, DPDPE, SNC80, morphine et deltorphine, contrairement au SB 235863 et le mcpTIPP. Une inhibition de l'internalisation du récepteur par
le dynasore prolonge la durée d'inhibition de l'AMPc pour tous les ligands, mais l'effet est plus marquant pour les agonistes
qui internalisent. Conclusion : Bref, ces données indiquent que l'internalisation contribue à la désensibilisation rapide du
récepteur, mais ce paramètre n'est pas un indicateur universel de la durée de la réponse à l'AMPc.
Contact information:
Centre de recherche du CHU Sainte-Justine,
3100, rue Ellendale, Montréal, QC, Canada, H3S 1W3
[email protected]
Page 9
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
2
ÉTUDE DU TRAFIC POST-ENDOCYTIQUE DU RÉCEPTEUR DELTA-OPIACÉ
I. CHARFI 1 , G. PINEYRO 2
1
Centre de recherche du CHU Sainte-Justine, Montréal, QC, Canada , 2Université de Montréal, Montréal, QC, Canada .
Les opiacés sont parmi les analgésiques les plus puissants pour le traitement des douleurs sévères. Les agonistes du récepteur
delta opiacé (DOR) induisent moins d'effets secondaires que ceux du récepteur mu, ce qui les rend une cible d'intérêt pour le
traitement des douleurs chroniques. Cependant, ils induisent la tolérance à l'analgésie. Des hypothèses récentes proposent que
le potentiel des drogues à induire la tolérance soit la conséquence d'une stabilisation de différentes conformations du
récepteur spécifiques du ligand, chacune ayant différentes propriétés de trafic soutenues par des mécanismes distincts. Dans
ce contexte, nous avons déterminé si différents ligands du DOR différaient par rapport à leur capacité à induire son trafic
post-endocytique (recyclage). En particulier, nous avons étudié le profil de recyclage du récepteur stimulé par différents
ligands et les mécanismes moléculaires sous-jacents. Les expériences ont été réalisées au niveau des neurones corticaux
transfectés avec le DOR et au niveau des cellules HEK-293 exprimant de façon stable le récepteur. Nos résultats indiquent
qu'au niveau des neurones, seulement le DPDPE, UFP-512 et TIPP réussissent à induire le recyclage du DOR (SNC-80 et
morphine ne le font pas). Le recyclage du DOR neuronal stimulé par le DPDPE est affecté par la température et dépend des
microtubules. Le récepteur co-localise avec le Rab4 et le Rab11 (deux marqueurs des compartiments cellulaires précoces et
tardifs, respectivement). Au niveau des cellules HEK-293, le recyclage du DOR stimulé par le DPDPE dépend de la
température et des microtubules et n'est pas sensible au Rab9 (responsable du trafic des endosomes tardifs au trans-Golgi).
Nos perspectives sont d'étudier les mécanismes de recyclage pour tous les ligands et de corréler ces profils de recyclage avec
le potentiel de tolérance analgésique de chaque drogue. Ces résultats permettraient le développement de ligands ayant une
activité analgésique plus durable.
Contact information:
Centre de recherche du CHU Sainte-Justine,
3100, rue Ellendale, Montréal, QC, Canada, H3S 1W3
[email protected]
Page 10
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
3
MÉCANISMES MOLÉCULAIRES DE LA TOLÉRANCE AUX OPIOÏDES : RÉGULATION
DU COMPLEXE CONSTITUTIF FORMÉ PAR LE RÉCEPTEUR OPIOÏDE DELTA ET LE
CANAL POTASSIQUE KIR3 PAR LA BARR2
K. NAGI 1 , I. CHARFI 1 , T. HÉBERT 2 , G. PINEYRO 1
1
Université de Montréal, Montréal, QC, Canada , 2Université McGill, Montréal, QC, Canada .
Introduction : Les opiacés figurent parmi les analgésiques les plus efficaces pour le traitement des douleurs sévères. Ces
analgésiques ciblent spécifiquement les récepteurs opioïdes. Des études ont révélé que le récepteur opioïde delta (ROD), la
protéine G et certains effecteurs atteignent la membrane comme une unité de signalisation. Face à ces observations, nous
proposons que les protéines régulatrices du ROD, comme la beta-arrestine (Barr), soient recrutées aux complexes plutôt
qu'aux récepteurs isolés. Ici, nous nous somme intéressés à étudier la régulation du complexe signalétique formé par ROD et
le canal potassique de la famille Kir3.
Méthodologie : Nous avons utilisé les techniques de co-immunopurification et BRET afin d'étudier l'interaction entre les
différents composants du complexe et la capacité du complexe à recruter la Barr. Cependant, les conséquences fonctionnelles
de ce recrutement sur l'internalisation du récepteur et du canal ont été caractérisées par les techniques d'ELISA et
d'immunocytochimie, réalisées respectivement sur des cellules HEK et des cultures primaires de neurones.
Résultats : Nos résultats montrent que le ROD, la protéine G et Kir3 restent associés suite à une activation soutenue (30 min)
avec les agonistes SNC-80 ou DPDPE. Nous avons également observé que la stimulation du ROD par le SNC-80 induit le
recrutement de la Barr2 vers ROD, les sous-unités Gbetagamma et le canal Kir3. Encore, on a établi que ROD et Kir3
exprimés dans les cultures primaires de neurones étaient à la fois internalisés non seulement suite à une stimulation par SNC80, mais aussi par la morphine. Enfin, nous avons observé que les ROD et les sous-unités des canaux Kir3 colocalisent avec
la Barr2 dans le compartiment intracellulaire.
Conclusion : Prises ensemble, ces données montrent que les ROD et les canaux Kir3 forment un complexe constitutif et
indiquent que la Barr2 les reconnaît comme une seule unité provoquant ainsi leurs internalisations simultanées.
Contact information:
Département de pharmacologie, Faculté de Médecine, Université de Montréal,
C.P. 6128, succursale Centre-ville, Montréal, QC, Canada, H3C 3J7
[email protected]
3DJH
Thème
Résumé no.
CANNABIS: REWARD AND PSYCHOSIS
Theme
Abstract no.
4
COCAINE-INDUCED IMPULSIVITY IS CURTAILED BY CB1 RECEPTOR BLOCKADE:
RAPID DOPAMINERGIC CORRELATES
G. HERNANDEZ
University of Maryland, Baltimore, MD, United States .
Impairment of decision-making processes is an important component of many psychological conditions, including addiction.
In humans and in non-human subjects tolerance to delay gratification can be studied using delay of reinforcement procedures.
In such paradigms, delayed rewarding outcomes are discounted hyperbolically; the subjective value of a rewarding outcome
depends on how distant in the future it is. Immediate rewarding outcomes have a greater subjective value than delayed ones,
and are always preferred over delayed ones. However, such preference can be reversed by increasing the value of the delayed
reward. When the larger, more delayed reward is chosen over the smaller, immediate reward, self-control has been exerted.
When the opposite occurs, impulsivity has taken place. When tested in laboratory tasks, individuals with substance abuse
problems as well as non-humans subjects under the influence of drugs of abuse, perform impulsively in tasks that assess selfcontrol. The present experiment examined the effects of a cocaine locomotor sensitization regime (10 mg/kg/i.p. on alternate
days) on self-control in rats and the blockade of this effect by the CB1 receptor antagonist rimonabant (1.5 mg/kg/i.p.). Rats
were trained to choose between one food pellet delivered immediately and four pellets delivered after varying delays, which
increased during the course of the session. Using this procedure, an increase in impulsivity was observed after cocaine
sensitization had taken place and in those rats pretreated with an i.p. injection of vehicle 30-min before cocaine injection.
Remarkably, this effect was absent in rats pretreated with an i.p. injection of rimonabant. Measurements of dopamine (DA)
release using fast-scan cyclic voltammetry showed that rimonabant-treated rats showed a robust increase in DA release for
the four pellets option at 0-s delay when compared with the 1 pellet option; but this trend reversed at 10-s delay, in which
more DA release was observed for the 1 pellet option. Vehicle-treated rats did not exhibit these patterns of release. These rats
showed a sustained increase in DA release for the one pellet option at the initial choice of 0-s delay. The results suggest that
CB1 blockade modulates accumbal dopaminergic encoding of changes in impulsivity produced by cocaine and that the
endocannabinoid system is crucially involved in the development and maintenance of enduring DA adaptations that result
from cocaine exposure.
Contact information:
Department of Anatomy and Neurobiology, University of Maryland,
20 Penn St, Room S251, Baltimore, MD, United States, 21201
[email protected]
Page 12
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
5
ACTIVATION OF VENTRAL MIDBRAIN NEUROTENSIN RECEPTOR SENSITIZES TO
AMPHETAMINE-INDUCED PHOSPHORYLATION OF EXTRACELLULAR SIGNAL
REGULATED KINASE
D. VOYER , D. LÉVESQUE , P. ROMPRÉ
Université de Montréal, Montréal, QC, Canada .
Previous studies have shown that neurotensin, an endogenous neuropeptide that modulates limbic neurotransmission, plays a
key role in the initiation of sensitization to behavioral effects of amphetamine. Blockade of neurotensin receptors prevents
amphetamine sensitization while repeated central neurotensin injections sensitize to amphetamine. Recently, we reported that
activation of ventral midbrain (VM) neurotensin receptor sensitizes to amphetamine-induced locomotor activity, an effect
prevented by blockade of ventral midbrain NMDA receptors. In this study, we used immunohistochemical technique to
measure phosphorylation of extracellular signal regulated kinase (pERK) in different limbic nuclei after VM injections of
neurotensin and after systemic amphetamine in animals pre-treated with VM neurotensin. Experiments were performed in
male Long-Evans rats implanted with VM bilateral canulae. Following three days of adaption, different groups of rats were
injected with vehicle-saline (0.5ul/side) or D-Tyr-11 neurotensin (1.5 nmol/0.5ul/side) every second day for three days and
with amphetamine sulphate (0.75 mg/kg, ip) five days after the last neurotensin injection. Rats were sacrified either 15 min
after first or the third VM microinjections, or after amphetamine, brains removed and pERK quantified in the prefrontal
cortex, nucleus accumbens (NAc, core and shell) and medial ventral tegmental area (VTA). Results show that neurotensin
enhances pERK within VTA after the first and the third VM neurotensine microinjection. Amphetamine increases pERK in
the NAc core and shell and the medial and lateral prefrontal cortex (mPFC and LPFC), and this increase was significantly
larger in the NAc shell, mPFC and LPFC in rats pretreated with neurotensin. These results suggest that activation of ERK
pathway within the VTA plays a role in the initiation of neurotensin induced amphetamine sensitization. They also suggest
that neurotensin is acting upstream in a pathway that initiate amphetamine sensitization. This work was supported by the
Canadian Institute for Health Research (CIHR).
Contact information:
Faculté de pharmacie, Université de Montréal,
C.P. 6128, succursale Centre-ville, Montréal, QC, Canada, H3C 3J7
[email protected]
3DJH
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
6
LIMBIC SYSTEM MGLUR5 ABNORMALITIES IN COCAINE DEPENDENT SUBJECTS: A
HIGH-RESOLUTION PET [11C]ABP688 STUDY
M. MILELLA 1 , L. MARENGO 1 , K. LARCHER 1 , A. FOTROS 1 , A. DAGHER 1 , P. ROSA-NETO 2 , C. BENKELFAT 1 , M. LEYTON 1
1
McGill University, Montréal, QC, Canada , 2Douglas Hospital, Montréal, QC, Canada .
Introduction: Cocaine self-administration leads to decreased type 5 metabotropic glutamate receptors (mGluR5) for a few
weeks in laboratory rats. These changes are thought to influence the varying ability of drug-related cues to precipitate relapse.
Here, our goal was to measure brain regional mGluR5 availability in cocaine dependent humans.
Methods: Eight cocaine users meeting DSM-IV criteria for current cocaine dependence and nine healthy controls (age and
sex matched) were recruited from the general population. Availability of mGluR5 (binding potential, BPND) was measured
with positron emission tomography (PET HRRT) and the high-affinity radioligand, [11C]ABP688. Anatomical MRIs were
obtained for co-registration purposes.
Results: Compared to controls, cocaine dependent subjects showed significantly reduced (~30%) BPND values in bilateral
ventral limbic striatum (left: p = 0.006; right: p = 0.03). Statistically significant reductions were also found in the left
amygdala, left lateral orbitofrontal cortex, left cingulate cortex and right insula. Receptor availabilities in the somatosensory
striatum and left amygdala were inversely correlated with duration of abstinence (range: 2-14 days) on the PET session (r = 0.72, p = 0.04).
Contact information:
Department of Psychiatry, McGill University,
845, rue Sherbrooke Ouest, Montréal, QC, Canada, H3A 2T5
[email protected]
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Theme
Abstract no.
7
ANIMALS WITH A SCHIZOPHRENIA-LIKE PHENOTYPE ARE DIFFERENTIALLY
SENSITIVE TO THE MOTIVATIONAL EFFECT OF CANNABINOIDS
A. GALLO , P. ROMPRÉ
Université de Montréal, Montréal, QC, Canada .
Cannabis is the most consumed illicit drug. According to the United Nation Office of Drugs and Crime, the rate of cannabis
consumption worldwide was between 2.6 and 5% in 2012. For the patients with a diagnosis of schizophrenia, cannabis
consumption in 5 to 10 times higher, and the reason for this remains obscure. Cannabis can produce both an aversive or a
rewarding effect and that raises the question: is cannabis more rewarding or less aversive in patients with schizophrenia? We
chose to study this question using a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions. A
first set of studies was aimed at validating the animal model. We compared the locomotor response to i) novelty, ii) a mild
stress and iii) two doses of amphetamine (0.75 and 1.5 mg/kg) in sham and lesioned rats at post-natal day 35 (PD35) or 56
(PD56). In a second set of studies, we investigated the valence of the motivational effect of delta-9-tetrahydrocannabinnol
(THC, 0.5 mg/kg, 1 ml/kg, ip) and the cannabinoid receptor agonist, WIN55,212-2 (WIN, 1 mg/kg, 3 ml/kg, ip), using the
conditioned place-preference paradigm. We used a biased procedure that comprised 12 consecutive days of testing:
habituation to the apparatus (Day 1-2), baseline preference test for one compartment (Day 3), THC or WIN (Day 4,7,10) and
vehicle (VEH;Day 5,8,11) conditioning, and preference test (Day 6,9,12). Results from the first studies showed that lesioned
rats had a stronger locomotor response to both doses of amphetamine than sham rats, an effect observed at PD56 only. The
second studies revealed that the cannabinoid agonist, WIN, produced a significant aversive effect in lesioned but not in sham
rats at PD56; this effect was not observed at PD35. At the dose tested, THC tended to produce an aversion in sham but not in
lesioned rats; THC pre-treated sham rats spent significantly more time in the neutral compartment than VEH pre-treated rats,
and this effect was observed at PD56 only. These results show that animals with a confirmed schizophrenia-like phenotype
are differentially sensitive to the motivational effect of cannabinoids, a phenomenon that occurs in adulthood only.
Differences observed with THC and WIN should be interpreted with caution as they are based on a single dose. Since THC is
the major active component of cannabis, it is tempting however to suggest that its aversive effect is blunted in schizophrenia,
a hypothesis that required testing a wider range of doses.
Contact information:
Département de physiologie, Université de Montréal,
C.P. 6128, succursale Centre-ville, Montréal, QC, Canada, H3C 3J7
[email protected]
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Résumé no.
Abstract no.
8
DIFFERENTIAL ROLES OF DORSAL STRIATUM AND PREFRONTAL CORTEX IN THE
PATHOGENESIS OF THE COGNITIVE SYMPTOMS OF SCHIZOPHRENIA
I. GANTOIS , T. POOTERS , B. VERMAERCKE , L. ARCKENS , R. D'HOOGE
Laboratory of Biological Psychology, Katholieke Universiteit Leuven, Leuven, Belgium .
The cognitive symptoms of schizophrenia (e.g., impaired executive functions, behavioural inflexibility) remain largely
intractable with available treatment. The striatum, the largest basal ganglia area, has been suggested to contribute to these
cognitive deficits. However, the specific role of striatal subareas and cortico-striatal pathways in cognitive (dys)functioning
remains unclear. Therefore, we presently studied learning and memory in mice with lesions in dorsomedial (DMS),
dorsolateral striatum (DLS), anterior cingulate cortex (aCC) and prelimbic/infralimbic areas (PL/IL). Animals were trained
for 15 days in the hidden-platform version of the Morris water maze. Compared to sham controls, animals with DMS damage
were impaired during acquisition training, displaying delayed spatial learning over all days, increased thigmotaxis, and
increased search distance to the platform. Animals with lesions in DLS, PL/IL and aCC also showed delayed spatial learning
during the 1st week of the task. Search strategy analysis indicated that the observed deficits coincided with a decrease in the
ability to switch flexibly between search strategies. In conclusion, our results suggest a differential role of striatal and
prefrontal cortex subareas in spatial learning and memory. These impairments suggest that specific cortico-striatal
connections are involved in the acquisition of goal-directed behaviours. It also shows that behavioural flexibility, a cognitive
function impaired in schizophrenia patients, is impaired in animals with striatal or prefrontal cortex lesions. The present
results could contribute to further understand the cognitive pathogenesis of schizophrenia.
Contact information:
Laboratory of Biological Psychology,
Department of Psychology and Educational Sciences, Katholieke Universiteit Leuven,
Tiensestraat 102, Leuven, Flemish Brabant, Belgium, B-3000
[email protected]
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Theme
Abstract no.
9
THE EFFECTS OF CANNABIS ABSTINENCE ON NEUROCOGNITIVE AND CLINICAL
SYMPOTOMS IN INDIVIDUALS WITH AND WITHOUT SCHIZOPHRENIA
R. RABIN 1 , C. STEFAN 1 , K. ZAKZANIS 2 , T. P. GEORGE 1
1
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada , 2University of Toronto Scarborough, Toronto, ON, Canada .
Background: Cannabis dependence is common in persons with schizophrenia (SZ) and related psychoses, and there is
evidence that cannabis misuse may hasten the onset of schizophrenia, and worsen positive, negative and neurocognitive
symptoms. The majority of data on neurocognition come from cross-sectional studies, and overall these studies show mixed
results; a meta-analysis of such studies controlling for other substance misuse suggested that cannabis use was associated
with modestly improved neurocognition in schizophrenia. The present study uses a controlled prospective design to
investigate the effects of cannabis abstinence from up to 28 days on psychotic and cognitive symptoms in cannabis dependent
person with schizophrenia versus non-psychiatric healthy control (HC) subjects. Methods: By study end, a total of 40
subjects (20 with SZ and 20 HC) will be enrolled in this study. To date we have enrolled six participants in the study (3 SZ, 3
HC). Participants undergoing cannabis abstinence were assessed at baseline, at Day 15 and Day 29 on neurocognition (tests
of executive function, working memory, speed of processing, motivation, verbal memory) and clinical symptoms (PANSS,
HDRS-17). Abstinence during the trial was assessed by self-report and twice weekly by objective measures. Urine specimens
were screened with a novel semi-quantitative assay (NarcoCheck) of cannabis from urine, and negative samples were
reinforced using low cost contingency management procedures. Urine samples were then tested by gas chromatography-mass
spectroscopy (GC-MS) to obtain quantitative THCCOOH levels, and normalized to creatinine concentrations. Participants
meeting both subjective and analytical criteria for cannabis abstinence were paid $300. Results: Our preliminary data
suggests the feasibility of these controlled cannabis abstinence procedures in an outpatient setting, and the pilot data on
cognitive and clinical outcomes from this nascent cohort of SZ and HC subjects undergoing one month of cannabis
abstinence will be presented. Conclusions: We have developed a novel and feasible approach to studying the effects of
extended cannabis abstinence in an outpatient setting in cannabis dependent subjects with and without schizophrenia. Our
approach may yield important new information on the effects of cannabis on cognitive and clinical outcomes in persons with
schizophrenia.
Contact information:
Schizophrenia Division, Centre for Addiction and Mental Health (CAMH),
250 College Street, Room 732, Toronto, ON, Canada, M5T 1R8
[email protected]
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Résumé no.
Abstract no.
10
EFFECTS OF NEUROTENSIN PEPTIDES ON VENTRAL MIDBRAIN NEURONS
P. BOSE , P. ROMPRÉ , R. WARREN
Université de Montréal, Montréal, QC, Canada .
Neurotensin (NT), an endogenous peptide that modulates limbic neurotransmission, plays a key role in the initiation of
sensitization to the behavioral effects of amphetamine. Repeated ventral midbrain (VM) injections of the NT analog, DTyr[11]NT, for instance, induce lasting increase in amphetamine-induced locomotor activity. The mechanism(s) by which
NT act(s) on VM neurons to induce sensitization remain(s) unclear. This study was aimed at characterizing the
electrophysiological effects of different NT fragments (NT1-13, NT 8-13 and D-Tyr[11]NT) on VM neurons. Long-Evans
male rats aged from 14 to 21 days were sacrificed and horizontal brain sections that spare VM afferent inputs were obtained.
Using in vitro patch-clamp technique, in the presence of GABAergic antagonist we have recorded more than 150 neurons and
measured excitatory post synaptic currents (EPSC) generated by the stimulation of the rostral VM afferents. Recorded
neurons were assigned to two different classes depending on their response to the injection of intracellular current steps from
a hyperpolarized holding membrane potential. One class, Ih-positive, displayed a prominent Ih current and the other class, Ihnegative, displayed no detectable Ih current. NT-1-13 and NT-8-13 both produced a concentration dependent increase in
EPSC in both Ih-positive and Ih-negative neurons while D-Tyr[11]NT produced an increase in Ih-negative neurons and a
decrease in Ih-positive neurons. The common excitatory effect of NT and the fragments on presumed non-DA neurons (Ihnegative) suggests that this mechanism may is relevant to the behavioral effects of the peptides and to the sensitization to
amphetamine. Preliminary results with SR142948A and DTyr11, the broad-spectrum NT antagonist, blocked both the
decrease and increase in EPSC amplitudes in Ih-positive and Ih-negative neurons respectively. Since D-Tyr[11]NT displays a
higher affinity for NTS2 than NTS1, we hypothesized that the differential effects observed with this analog is meditated by
the former sub-type of receptors, a hypothesis that is currently being investigated.
Contact information:
Département de psychiatrie, Université de Montréal,
C.P. 6128, succursale Centre-ville, Montréal, QC, Canada, H3C 3J7
[email protected]
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Résumé no.
Abstract no.
11
PAVLOVIAN-CONDITIONED ALCOHOL-SEEKING IN RATS IS REDUCED BY NBQX
ADMINISTRATION IN THE BASOLATERAL AMYGDALA
J. SCIASCIA
Center for Studies in Behavioural Neurobiology (CSBN), Concordia University, Montréal, QC, Canada .
Rationale Environmental cues associated with alcohol consumption can trigger craving and facilitate relapse in abstinent
alcoholics. Objectives We tested the hypothesis that the environmental context in which a Pavlovian-conditioned, alcohol cue
is encountered influences the strength of conditioned alcohol-seeking triggered by the cue. We also investigated the
contribution of AMPA glutamate receptors in the basolateral amygdala (BLA) to Pavlovian-conditioned alcohol-seeking in
an alcohol-associated context and a context where alcohol had never been consumed. Methods Male, Long-Evans rats that
had previously consumed ethanol (EtOH; 15%; v/v) in the home-cage received Pavlovian conditioning sessions in which a
10-sec auditory conditioned stimulus (CS+; white noise; 15 trials per session) was paired with EtOH (0.2 ml per CS+; 3 ml
per session) for oral consumption. Entries into a fluid port where EtOH was delivered were measured. Rats were trained to
discriminate between a context where alcohol was consumed and a non-alcohol context by conducting conditioning sessions
every other day in a specific environmental context referred to as Context A. In between these sessions, rats were exposed to
a different context (Context B) where the CS+ and EtOH were never presented. At test, the CS+ was presented without EtOH
in either the alcohol-associated context (Context A) or the non-alcohol context (Context B), using a within-subject design. In
a separate study rats received a bilateral microinfusion (0.3 μl/hemisphere) into the BLA of saline, 1.0 or 5.0 μg of the
AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor antagonist NBQX [2,3-dihydroxy-6-nitro-7sulfamoyl-benzo[f]quinoxaline-2,3-dione)]. Results Port-entries elicited by the CS+ increased across conditioning sessions.
At test, rats responded more to the CS+ in the alcohol-associated context, compared to the non-alcohol context. NBQX
attenuated CS+ responding at test in both contexts. Port entries during the 10 sec interval following the CS+ presentation was
significantly attenuated in the non-alcohol context but not in the alcohol context. Conclusion These data highlight an
important role of context in modulating the vigour of Pavlovian-conditioned alcohol-seeking, and suggest that AMPA
receptors within the BLA are required for the expression of this behaviour. [Supported by NIAAA, RO1AA14925
(PHJ);FRSQ (NC)]
Contact information:
Center for Studies in Behavioral Neurobiology (CSBN),
Department of Psychology, Concordia University,
7141, rue Sherbrooke Ouest, Montréal, QC, Canada, H4B 1R6
[email protected]
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Résumé no.
Abstract no.
12
NICOTINE ENHANCES PAVLOVIAN CONDITIONED RESPONDING TO AN ETHANOLASSOCIATED CUE IN RATS
J. MADDUX , F. LACROIX , N. CHAUDHRI
Center for Studies in Behavioural Neurobiology (CSBN), Concordia University, Montréal, QC, Canada .
Cues associated with drug use can gain powerful control over drug-seeking and drug-taking behaviour through Pavlovian
conditioning. Furthermore, nicotine has been found to enhance responding to a Pavlovian cue associated with a natural
reward, water, in water-restricted rats. Given that nicotine and alcohol are commonly co-abused drugs, the purpose of this
study was to determine if nicotine also increased the acquisition of responding to a Pavlovian cue associated with alcohol in
non-restricted rats.
Male, Long-Evans rats were acclimated to the taste and pharmacological effects of 15% ethanol in their home-cages.
Subsequently, rats were trained in a Pavlovian conditioning paradigm in which a 15 second compound conditioned stimulus
(CS) was paired with 0.2 ml of 15% ethanol (unconditioned stimulus; US) into a fluid port in the conditioning chamber (12
trials/session; 2.4 ml EtOH/session). To assess conditioning the number of port entries during a pre-CS baseline was
subtracted from port entries during the corresponding CS to create a normalized CS port entry measure. Importantly, a
control group that received explicitly unpaired presentations of the CS and US was included to determine if observed
nicotine-induced changes in behaviour were due to associative or non-associative processes. Before each training session, rats
received an injection of either saline or nicotine (0.4 mg/kg, freebase), according to their assigned treatment and conditioning
groups. A second experiment investigated the effects of the nicotinic acetylcholine receptor antagonist, mecamylamine (2.0
mg/kg), on conditioned port entry responses to an ethanol-predictive cue. All rats had unrestricted access to food and water.
Rats in the paired group acquired conditioned port entry responding to the CS, indicative of Pavlovian ethanol-seeking,
whereas rats in the unpaired control group did not. Moreover, nicotine increased CS port entry responses relative to saline
only in the paired group, suggestive of action on an associative mechanism. In contrast, mecamylamine decreased CS port
entry responses relative to saline, suggesting that nicotinic acetylcholine receptor activation is necessary to acquire normal
levels of Pavlovian ethanol-seeking.
These findings imply that nicotine contributes to the formation of cue-alcohol associations. Individuals who smoke and drink
may thus be particularly susceptible to alcohol cues that could trigger further drinking.
Contact information:
Center for Studies in Behavioural Neurobiology (CSBN)
Department of Psychology, Concordia University,
7141, rue Sherbrooke Ouest, Montréal, QC, Canada, H4B 1R6
[email protected]
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Résumé no.
Abstract no.
13
THE RELATION TO DRUG USE AND THE FIRST PSYCHIATRIC HOSPITALIZATION
FOR PSYCHOTIC EPISODE
B. C. CICCONE GIACON , S. A. FRARI GALERA , T. GRANADOS FERRARI , M. R. SELEGHIM , I. DOS SANTOS MARTIN
Department of Psychiatric Nursing and Human Sciences, University of São Paulo at Ribeirão Preto College of Nursing, São Paulo, Brazil .
The aim of this study is to describe the personal, demographic and clinical data association of patients who have had their
first psychiatric hospitalization due to psychotic episode, with use of drug's presence or not. Documental and descriptive
study, developed in three hospitals in Ribeirão Preto, São Paulo, Brazil. Based on the analysis of all patients' records, who
suffered a first psychiatric hospitalization in the year 2011, we identified that 44 patients of them were hospitalized due to the
first psychotic episode. The variables analyzed were: gender, age, city of origin, care service, length of hospitalization,
diagnostic hypothesis, drug use, major signs /symptoms and service care reference. The data's statistical analyze was
conducted using the Statistical Analysis System ® 9.1, with 0.05% of significance. Most adolescent who suffered the first
hospitalization for psychosis were men (82.0%), with age between 20-25 years (59%), that have had the first attendance in
emergency psychiatric service (65.9 %), and remained hospitalized for 30 days (75%). The reports of psychoactive substance
use have presented on 25 (56,9) patients' records, the use of mainly marijuana (15 patients), cocaine /crack (20 patients) and
alcohol (5 patients). On 19 patients' records the diagnosis of psychosis was related to drug use. Concerning the association of
personal, demographic and clinical data, with the presence or not of the use of drugs, we found significant relation in gender
(p-value 0.044), age (p-value 0.001), and care service (p-value 0.001). Studies investigating the use of drugs among patients
with schizophrenia indicate that men present greater propensity for the use of drugs than women, and that people with a
familiar historic of schizophrenia or psychotic disorders who also make use of drugs are more vulnerable to develop a mental
disorder. The results analyzed in this study demonstrate the importance of comprehending the relationship between drug use
and the first psychotic episode, especially in groups with a genetic predisposition for schizophrenia. It also shows the need
for early identification of risk and protective factors for the development of psychosis, especially regarding drug use in men
and psychiatric emergency care. Greater knowledge of this relationship can contribute to the development of strategies,
which facilitate the identification of people at risk, to allow early intervention with the sufferers and their families.
Contact information:
Department of Psychiatric Nursing and Human Sciences,
University of São Paulo at Ribeirão Preto College of Nursing,
Avenida dos Bandeirantes, 3900, Ribeirão Preto, São Paulo, Brazil, 14040-902
[email protected]
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Résumé no.
Abstract no.
14
DEFICITS IN THETA-GAMMA COUPLING IN NICOTINE DEPENDENT PATIENTS WITH
SCHIZOPHRENIA
M. S. BARR , R. ZOMORRODI 1 , V. C. WING 2 , K. M. MACKOWICK 2 , Z. J. DASKALAKIS 1 , T. P. GEORGE 2
1
Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada , 2Biobehavioural Addictions
and Concurrent Disorders Laboratory, Schizophrenia Program, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada .
Patients with schizophrenia smoke more cigarettes compared to the general population. This increased prevalence may be
related to the pathophysiology of this disorder and possible remediation of cognitive deficits such as working memory.
Working memory represents a core deficit in patients with schizophrenia that is associated with excessive gamma (30-50 Hz)
oscillatory activity. In addition to gamma, working memory has been shown to depend on theta (4-7 Hz) oscillatory activity-a
mechanism referred to as theta-gamma coupling. It is proposed that the relationship between theta phase and gamma
amplitude is critical to how different items are both encoded and maintained during working memory performance. In
patients with schizophrenia, preliminary evidence demonstrates that deficits in working memory performance are associated
with deficits in theta-gamma coupling. Evaluation of theta-gamma coupling in nicotine dependent patients with
schizophrenia may help to further understand the neurophysiological underpinnings of working memory and determine if
smoking remediates such deficits. In this study, therefore, theta-gamma coupling was evaluated during the N-back task in six
patients with schizophrenia compared to seven healthy subjects who were all nicotine dependent. Theta-gamma coupling was
found to be significantly reduced in patients with schizophrenia compared to healthy subjects. This deficit was selective to
the 3-back load, the task of greatest difficulty. No differences in N-back performance were found between patients with
schizophrenia compared to healthy subjects. These findings add to the evidence for theta-gamma coupling deficits in patients
with schizophrenia, but suggest that cigarette smoking may remediate working memory deficits in this disorder.
Supported in part by CIHR operating grant MOP#115145 to Dr. George
Contact information:
Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health (CAMH),
1001 Queen Street West, Toronto, ON, Canada, M6J 1H4
[email protected]
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Résumé no.
Abstract no.
15
CUE REACTIVITY IN SMOKERS WITH SCHIZOPHRENIA: A PILOT STUDY
A. BRIDGMAN 1, 2 , K. M. MACKOWICK 1, 2 , V. C. WING 1, 2 , T. P. GEORGE 1, 2
1
University of Toronto, Toronto, ON, Canada , 2Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada .
Background: Exceptionally high smoking rates are reported in patients with schizophrenia (SZ) (60-90%) compared to the
general population. Understanding the link between high smoking rates and cue reactivity (CR) in this population may inform
development of tobacco treatments, given that CR may predict smoking relapse. The present study uses a cross-sectional
design to investigate cue-induced craving in response to neutral and smoking in vivo cues in SZ patients with co-morbid
tobacco addiction versus healthy controls (HC) with tobacco addiction. Methods: To date a total of 14 participants have
completed this study (n=7 SZ; n=7 HC). CR sessions lasted 11 minutes, while participants were satiated (smoking 5 minutes
prior). Sessions consisted of a 3-minute baseline, followed by exposure to the neutral cue (pencil and eraser), a washout
period of 5 minutes, and then exposure to the smoking cue (participant's cigarette and lighter). A visual analog scale (VAS)
was administered before and after each cue condition, and each cue was presented for 90 seconds. Results: 4/7 smokers met
criteria for smoking CR in the control group, and 4/7 in the schizophrenia group (defined as VAS change >0 for smoking CR
minus neutral cues CR). Mean smoking CR scores (smoking CR - neutral CR) for SZ (6.9+8.6 mm) and HC (15.4+13.5 mm)
were not significantly different [t(6)=1.06, p=0.33]. Conclusions: This data suggest that this in vivo cue reactivity paradigm
was effective in inducing smoking CR in smokers with and without SZ. These findings may have implications for developing
improved tobacco treatments for people with schizophrenia.
Contact information:
Schizophrenia Division, Centre for Addiction and Mental Health (CAMH),
University of Toronto,
250 College Street, Toronto, ON, Canada, M5T 1R8
[email protected]
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Résumé no.
Abstract no.
16
CIGARETTE SMOKING TOPOGRAPHY: EVIDENCE FOR INCREASED SMOKING
REINFORCEMENT IN SMOKERS WITH SCHIZOPHRENIA
K. M. MACKOWICK , V. C. WING , A. TALPUR , T. P. GEORGE
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada .
Background: Cigarette smoking is the leading preventable cause of death in the Western world. People with schizophrenia
are more likely to smoke than those in the general population, smoke more cigarettes per day, are more nicotine dependent,
and have higher levels of expired breath carbon monoxide (CO). Smokers with schizophrenia have also shown increased
measures of reinforcement using smoking topography, such as more puffs per cigarette, larger puff volumes, and shorter inter
puff intervals. Because of the propensity to smoke more cigarettes, compounded by low quit rates, effective smoking
cessation methods are needed for those with schizophrenia. The purpose of this study was to examine measures of smoking
topography in the context of a larger study determining the effects of repetitive transcranial magnetic stimulation (rTMS) on
tobacco measures and cognition in schizophrenia.
Methods: Participants (N=20) smoked at least 10 cigarettes per day, were between the ages of 18 and 55, and had an Axis I
diagnosis of schizophrenia or schizoaffective disorder (SCZ; N=12) or no Axis I diagnosis (CTL; N=8). All participants
smoked one ad-lib cigarette through a CReSS Mirco topography device after approximately one hour of withdrawal.
Results: We found that, while current smoking rates did not differ between the two groups, SCZ smoked more cigarettes per
day when at their heaviest smoking rate than CTL. SCZ also showed significant positive correlations between the average
number of cigarettes smoked at the onset of their smoking and various measures of topography (number of puffs, puff
volume, and puff duration). Additionally, SCZ showed significant positive correlations between Fagerstrom Test for Nicotine
Dependence (FTND) scores and tobacco exposure (pack-years), and cigarettes smoked per day. CTL smokers showed
significant positive correlations between average number of cigarettes per day at the onset of smoking, and total puff volume
and average puff volume. No relationship was observed between FTND and other smoking variables in CTL.
Conclusions: These results suggest that smokers with schizophrenia display increased measures of smoking reinforcement
compared to non-psychiatric smokers, and may have implications for developing novel cessation strategies for smokers with
schizophrenia.
Contact information:
Schizophrenia Division,
Centre for Addiction and Mental Health (CAMH),
250 College Street, , Room 732, Toronto, ON, Canada, M5T 1R8
[email protected]
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Résumé no.
Abstract no.
17
CRAVING FOR CIGARETTES IN FEMALE SMOKERS IS MENSTRUAL CYCLE PHASE
DEPENDENT: AN FMRI STUDY
A. MENDREK 1 , J. BOURQUE 2 , S. POTVIN 3
1
Bishop's University, Sherbrooke, QC, Canada , 2Université de Montréal, Montréal, QC, Canada , 3Centre de recherche Fernand-Seguin, Montréal, QC,
Canada .
Although the number of smokers is gradually decreasing in developed countries, the decline has been less pronounced in
women than in men. In fact, epidemiological studies suggest that cigarette smoking is on the rise in young women and teen
girls. Among adults still more men than women smoke, but women take less time to become dependent after initial use,
report shorter and less frequent abstinence periods and overall have more difficulties quitting the habit, than men. One of the
factors contributing to these differences may be that women crave cigarettes more than men. Indeed, some preclinical and
clinical studies suggest that craving for various drugs of abuse is greater in females than in males and that it may be
influenced by hormonal fluctuations across the menstrual cycle in women (or estrous cycle in rats). Therefore, the main
purpose of the present study was to delineate the neural correlates of cigarette cravings in women across their menstrual cycle
(during the follicular versus the luteal phase).
Fourteen tobacco-smoking women underwent a functional magnetic resonance imaging (fMRI) during early follicular (low
levels of estradiol and progesterone) the mid-luteal (high levels of estradiol and progesterone) stage of their menstrual cycle,
while passively viewing blocks of neutral images and blocks of cigarette-related images to elicit craving. Participants
reported subjective ratings of craving for each picture.
Analysis of the fMRI data collected in the follicular phase of the menstrual cycle revealed significant activations during
craving (relative to neutral) condition in the medial superior frontal gyrus, anterior and middle cingulate, as well as
precuneus. In comparison, the activations during the luteal phase were restricted only to hippocampus. Despite the lack of
statistically significant differences in subjective ratings for cigarettes craving between the two phases of the menstrual cycle,
there was a trend consistent with the fMRI data - greater cravings during the follicular relative to the luteal phase.
The main finding of the present study is that women appear to crave cigarettes more strongly during the follicular relative to
the luteal phase of their menstrual cycle. This may be related to the differential levels of estradiol and/or progesterone during
these two phases and we are currently exploring this possibility. Present findings may provide some preliminary clues to
design better programs to quit smoking for women.
Contact information:
Psychology Department, Bishop's University,
2600, College, Sherbrooke, QC, Canada, J1M 1Z7
[email protected]
3DJH
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
18
EFFECTS OF CIGARETTE SMOKING AND VARENICLINE ON SENSORIMOTOR GATING
IN PATIENTS WITH SCHIZOPHRENIA VERSUS CONTROLS: A PRELIMINARY STUDY
M. MOROZOVA , C. E. WASS , V. C. WING , T. P. GEORGE
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada .
Schizophrenia (SCZ) is associated with cognitive dysfunction including sensorimotor gating deficits. Nicotine through
cigarette smoking may improve sensorimotor gating such as pre-pulse inhibition (PPI; suppression of response to a stimulus
when preceded by a weaker stimulus) and habituation (tendency for response to decrease with repeated stimulus
presentation). We evaluated the effects of varenicline (a nAChR partial agonist) on sensorimotor gating in SCZ and control
(CON) smokers.
PPI and habituation were assessed in SCZ (n=8) and CON (n=8) smokers in a cross-over, placebo-controlled, double-blind
study at baseline smoking and following overnight cigarette smoking abstinence and reinstatement, while treated with 3
doses of varenicline tartrate (Champix®; 0, 0.5 or 1.0 mg BID). Startle to auditory stimuli was measured as obicularis oculi
electromyographic activity. PPI was measured at 30, 60 and 120ms stimulus onset asynchronies (SOA).
Baseline PPI and habituation tended to be lower in SCZ versus CON, which trended towards significance at SOA30
[t(14)=1.98, p=.07]. Abstinence appeared to decrease, and reinstatement to increase, SOA60 PPI in the placebo week in SCZ
and varenicline disrupted this; these effects did not reach significance. There was a significant effect of smoking on
habituation in the placebo, but not varenicline, treatment weeks in SCZ, resulting from increased habituation in abstinence
[F(2, 21)=3.63, p=.04]; there was no effect on habituation in CON.
These preliminary results demonstrate that SCZ smokers display nicotine-sensitive PPI deficits and that habituation may be
modified in SCZ via nicotinic receptor mechanisms. Targeting nAChR systems may prove useful for treating cognitive
dysfunction in SCZ.
Supported in part by an operating grant from the Ontario Mental Health Foundation (OMHF) and CIHR Operating Grant
MOP#115145 to Dr. George.
Contact information:
Schizophrenia Division, Centre for Addiction and Mental Health (CAMH),
250 College Street, CS 734, Toronto, ON, Canada, M5T 1R8
[email protected]
Page 26
Thème
Theme
PSYCHOSTIMULANTS AND NICOTINE: REWARD,
SYNAPTIC PLASTICITY, AND PSYCHIATRIC DISEASE
Résumé no.
Abstract no.
19
A HUMAN LABORATORY STUDY OF THE EFFECTS OF VARENICLINE ON TOBACCO
CRAVING AND WITHDRAWAL IN SMOKERS WITH SCHIZOPHRENIA VERSUS
CONTROLS
C. OUELLET-PLAMONDON , V. C. WING , C. E. WASS , A. TALPUR , A. AZIZIYEH , T. P. GEORGE
Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada .
Background: Varenicline is a nicotinic acetylcholine receptor partial agonist and an effective tobacco pharmacotherapy in
non-psychiatric control smokers (CON) and those with schizophrenia (SZ). It reduces craving and withdrawal in CON
smokers but its effects in SZ are less well-studied.
Objective: To utilize a laboratory paradigm to evaluate the effects of varenicline on tobacco craving and withdrawal in SZ
and CON smokers under smoking as usual, overnight abstinence and reinstatement conditions. Methods: A total of N=26
nicotine dependent cigarette smokers (SZ; n=13 and CON; n=13) were assessed on the Minnesota Nicotine Withdrawal Scale
(MNWS) and Tiffany Questionnaire for Smoking Urges (TQSU) while smoking ad libitum, following biochemically verified
overnight abstinence (16 hours), and after reinstatement of smoking. This was repeated across three separate test weeks,
during which participants were pretreated in a double-blind counterbalanced manner with varenicline (0, 0.5 or 1 mg BID x 3
days).
Results: Robust effects of smoking abstinence and reinstatement were observed on TQSU and MNWS craving scores in SZ
and CON smokers (p<0.001). The higher dose of varenicline (1mg BID) attenuated abstinence-induced increases in craving
in CON (p<0.01) but not SZ smokers.
Conclusion: A 3-day varenicline treatment regimen reduces craving during tobacco abstinence in non-psychiatric control
smokers, but has limited effects in smokers with SZ. Varenicline's ability to increase smoking cessation rates in SZ may be
related to effects on other aspects of tobacco dependence and withdrawal such as neurocognitive modulation.
Supported in part by grants from the Ontario Mental Health Foundation (OMHF, to Dr. George) and CIHR MOP#115145
(Dr. George)
Contact information:
Schizophrenia Division, Centre for Addiction and Mental Health (CAMH),
250 College Street, Room 727, Toronto, ON, Canada, M5T 1R8
[email protected]
3DJH
Ordre des présentations affichées / Order of poster presentations
No.*
Premier auteur/First author
Page
1
BAGHERI, Haniyeh
9
2
CHARFI, Iness
10
3
NAGI, Karim
11
4
HERNANDEZ, Giovanni
12
5
VOYER, David
13
6
MILELLA, Michele
14
7
GALLO, Alexandra
15
8
GANTOIS, Ilse
16
9
RABIN, Rachel
17
10
BOSE, Poulomee
18
11
SCIASCIA, Joanna-Marie
19
12
MADDUX, Jean-Marie
20
13
CICCONE GIACON, Bianca Cristina
21
14
BARR, Mera S.
22
15
BRIDGMAN, Alanna
23
16
MACKOWICK, Kristen M.
24
17
MENDREK, Adrianna
25
18
MOROZOVA, Marya
26
19
OUELLET-PLAMONDON, Clairelaine
27
* Numéro de la présentation affichée
* Number of the poster presentation
3DJH
Liste alphabétique des premiers auteurs / Alphabetical list of first authors
Premier auteur/First author
No.*
Page
1
9
BARR, Mera S.
14
22
BOSE, Poulomee
10
18
BRIDGMAN, Alanna
15
23
2
10
13
21
GALLO, Alexandra
7
15
GANTOIS, Ilse
8
16
HERNANDEZ, Giovanni
4
12
MACKOWICK, Kristen M.
16
24
MADDUX, Jean-Marie
12
20
MENDREK, Adrianna
17
25
6
14
18
26
3
11
19
27
9
17
11
19
5
13
BAGHERI, Haniyeh
CHARFI, Iness
CICCONE GIACON, Bianca Cristina
MILELLA, Michele
MOROZOVA, Marya
NAGI, Karim
OUELLET-PLAMONDON, Clairelaine
RABIN, Rachel
SCIASCIA, Joanna-Marie
VOYER, David
* Numéro de la présentation affichée
* Number of the poster presentation
3DJH
Liste alphabétique complète des auteurs / Complete alphabetical list of authors
Auteur/Author
ARCKENS, Lut
AZIZIYEH, Adel
BAGHERI, Haniyeh
BARR, Mera S.
BENKELFAT, Chawki
BOSE, Poulomee
BOURQUE, Josiane
BRIDGMAN, Alanna
CHARFI, Iness
CHAUDHRI, Nadia
CICCONE GIACON, Bianca Cristina
D'HOOGE, Rudi
DAGHER, Alain
DASKALAKIS, Zafiris J.
DOS SANTOS MARTIN, Isabela
FOTROS, Aryan
FRARI GALERA, Sueli Aparecida
GALLO, Alexandra
GANTOIS, Ilse
GEORGE, Tony P.
GRANADOS FERRARI, Taisi
HERNANDEZ, Giovanni
HÉBERT, Térence
LACROIX, Franca
LARCHER, Kevin
LEYTON, Marco
LÉVESQUE, Daniel
No.*
8
19
1
14
6
10
17
15
2, 3
12
13
8
6
14
13
6
13
7
8
9, 14, 15,
16, 18, 19
13
4
3
12
6
6
5
Auteur/Author
MACKOWICK, Kristen M.
MADDUX, Jean-Marie
MARENGO, Laura
MENDREK, Adrianna
MILELLA, Michele
MOROZOVA, Marya
NAGI, Karim
OUELLET-PLAMONDON, Clairelaine
PINEYRO, Graciela
POOTERS, Tine
POTVIN, Stéphane
RABIN, Rachel
ROBERTSON, Derek
ROMPRÉ, Pierre-Paul
ROSA-NETO, Pedro
SCIASCIA, Joanna-Marie
SELEGHIM, Maycon Rogério
STEFAN, Cristiana
TALPUR, Anushka
VERMAERCKE, Ben
VOYER, David
WARREN, Richard
WASS, Caroline E.
WING, Victoria C.
ZAKZANIS, Konstantine
ZOMORRODI, Reza
No.*
14, 15, 16
12
6
17
6
18
3
19
1, 2, 3
8
17
9
1
5, 7, 10
6
11
13
9
16, 19
8
5
10
18, 19
14, 15, 16,
18, 19
9
14
* Numéro de la présentation affichée
* Number of the poster presentation
3DJH
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