Hallberg for web.pptx

2013-11-29
Anti Doping Denmark, Research seminar
November 26 2013, Copenhagen
FACULTY
OF PHARMACY
Brain and Anabolic steroids
Mathias Hallberg, Associate professor
Department of Pharmaceutical Biosciences
Division of Biological Research on Drug Dependence
FACULTY
OF PHARMACY
Headlines in media
Doping
22 year old bodybuilder killed her husband
Han skulle bara ta en kort kvällspromenad och rasta hunden.
Klockan var runt fem, hustrun stod med maten på spisen. Ingvar
kom aldrig hem. En 22-årig kroppsbyggare – fullproppad med
anabola steroider – stod i vägen.”
e
ated wif
V ill-tre en hjälte.
T
m
o
fr
av.
r
rn
tormasken
Gladiato
e gladiato
g
dia
en 36-åri
v
tsade gla
I tv var d a åkte den tv-pu ingbrott och gro
p
m
o
d
r
em
h
fö
ad
Men
sl
g
n
fä
han
Nu sitter
ning.
idskränk
Kvinnofr
Fredrik, made Fred
rik craz
1
senare: 5 år: normalby
y
ggd
upp
blev kax umpad, testost och 70 kilo tun
eronstin
ig och m
n och 13 g. Några år
Jag måd
allig, m
0
en
de bra h
elt enkel också utåtrikta kilo. – Jag
t. Tio år
d
senare k och glad.
om smäl
len.
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removed
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FACULTY
OF PHARMACY
Desirable effects
Increased muscle mass
Increased muscular strength
Increased energy
-----Increased self-esteem
Aggression
FACULTY
OF PHARMACY
Anabolic steroids affects the brain
Brain
Euphoria
Increased self-esteem
Increased energy
Increased motivation
Aggression
Risk of violent actions
Irritability
impulsivity
Anxiety
Depression
Psychosiss
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FACULTY
OF PHARMACY
Common steroids on the market
OH
O
OH
N
O
Testosterone
OH
Nandrolone
N
H
Stanozolol
OH
OH
O
O
Methandrostenolone
Tetrahydrogestrinone (THG)
FACULTY
OF PHARMACY
Physical effects of anabolic steroids
  Gynecomastia
  Baldness
  Striae
  Testicular atrophy
  Cardiovascular diseases
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FACULTY
OF PHARMACY
Steroid 1
Steroid 2
Steroid 3
Week 1
10 mg/day
Week 2
10 mg/day
Week 3
10 mg/day
Week 4
10 mg/day
200 mg
Week 5
10 mg/day
200 mg
Week 6
10 mg/day
200 mg
Week 7
10 mg/day
200 mg
300 mg
Week 8
10 mg/day
200 mg
300 mg
Week 9
200 mg
300 mg
Week 10
200 mg
300 mg
Week 11
300 mg
Week 12
300 mg
HCG
Week 13
7500 - 10 000 IU
Week 14
5000 – 7500 IU
Week 15
5000 IU
* Besides steroids and HCG, other substances that may
minimize side-effects are recommended.
FACULTY
OF PHARMACY
Testosterone and the main metabolism
OH
OH
1
O
O
Testosterone
Testosterone
2
HO
Estradiol
Estrogen
H
Dihydrotestosterone
Dihydrotestosterone
OH
Receptors
(targets)
1) 5α-reductase
2) aromatase
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FACULTY
OF PHARMACY
Common substances
Enzym inhibitors (inhibits the estrogen production)
Anti-estrogens
hCG
β2-agonists (luftrörsvidgande)
Growth hormone
Stimulants
Analgesics (opiates)
Benzodiazepins
-------------------------------------------------Narcotics and poly-drug use is frequently reported
Source: e.g Skårberg et al 2008
Subst Abuse Treat Prev Policy 3:24
FACULTY
OF PHARMACY
Brain reward system
GABA interneuron
Endorphin
Enkephalin
Dopamine neuron
Dopamine
Dynorphin
Nucleus accumbens
VTA
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FACULTY
OF PHARMACY
fmol/mg tissue
Anabolic steroids increase the levels of β-endorphin
in the drug reward system
Control
AAS
5mg/kg
AAS
15mg/kg
Source: Johansson et al., 1997.
Neurosci Res 27: 185-189
FACULTY
OF PHARMACY
Anabolic steroids affect the dynorphin as well as
dopamine receptors
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removed
Source: Magnusson et al., 2009.
Neuropeptides 43:105-111
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removed
Source: Kindlundh et al., 2001.
Eur J Neurosci (13) 291-296
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FACULTY
OF PHARMACY
ethanol intake [g/kg/dag]
The effect of AAS on alcohol intake
*
1.0
*
AAS
Control
0.5
0.0
vecka 1
vecka 2
vecka 3
Source: Johansson et al., 2000
Pharmacol Biochem Behavior 67: 271-279
FACULTY
OF PHARMACY
AAS may induce a mild dependency (including both
psychological and biological components)
Self-administration
of testosterone is blocked by dopamine
receptor antagonists #
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removed
Source: Wood RI (2008) Front neuroendocrinol. 29 (4):490-506
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FACULTY
OF PHARMACY
AAS as a gateway to drug dependence
Harrison G Pope and co-workers:
1990: One (0,5 %) of 197 heroin addicts has a history of AAS
1999: 21 (9,3 %) of 227 heroin addicts have a history of AAS
2003: 22 (25 %) of 88 heroin addicts have a history of AAS
FACULTY
OF PHARMACY
Anabolic androgenic steroids and
criminality
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removed
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FACULTY
OF PHARMACY
Reactivity score
AAS treated rats are more aggressive
***
4
2
0
AAS
AAS
Kontroll
Controls
Source: Lindqvist et al 2002
FACULTY
OF PHARMACY
Competition: AAS treated rats are more dominant
Basline
Competition
Drinking time (sec)
350
300
250
**
200
150
100
50
0
AAS
Control
Source: Lindqvist et al 2002
Behav Brain Res, 133: 21-29
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FACULTY
OF PHARMACY
Pathways in aggression
Source: Bitran et al 1996; Hallberg et al 2005; Hallberg
et al 2000; Kindlundh et al 2003; LeGreves et al 1997
FACULTY
OF PHARMACY
Conclusion
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removed
Source: Nyberg and Hallberg, 2012
Int Rev Neurobiol 102:181-198
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FACULTY
OF PHARMACY
Thank you for listening!
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