Evan Hale - Sample Research Abstract

Evan Hale - Sample Research Abstract
This is an expanded form of the abstract from my Extended Essay in Biology for the
International Baccalaureate Diploma Program, titled "The Role of γ-Aminobutyric Acid in
Ethanol Preference Development in Caenorhabditis elegans." This research project was
conducted under the supervision of Dr. Julie Nowicki, Mrs. Danielle Jensen, and Dr. Linda
Rogers, teachers at Biotechnology High School, during the 2012-2013 school year.
C. elegans is a nematode commonly used in neuroscience studies as an animal model
organism. Its nervous system is highly studied and well-characterized, and includes many
neurotransmitters also present in humans, including dopamine, glutamate, and γ-aminobutyric
acid (GABA) (Riddle et al., 1997). GABA is the major inhibitory neurotransmitter in the central
nervous system; it causes the postsynaptic neuron to hyperpolarize so that it is less likely to
transmit an action potential (creating an inhibitory postsynaptic potential [IPSP]) (Purves et al.,
2001). Numerous studies have implicated GABA receptors as key in the human addiction
pathway (Filip & Frankowska, 2008).
Ethanol is the most commonly abused addictive substance; approximately 9% of
American adults meet the criteria for an alcohol use disorder according to the National
Epidemiologic Survey of Alcohol and Related Conditions (Falk et al., 2008). Ethanol is a
GABAA agonist, meaning that it acts on GABAA receptors to amplify the inhibitory effects of
GABA. This depresses the activities of some neurological systems, resulting in symptoms like
ataxia, poor judgment, stupor, and depressed respiratory rate (at high blood concentrations). It is
thought that alcohol reacts via two major mechanisms to produce addiction. One mechanism
involves potassium channels; some studies have shown that ethanol excites dopaminergic
neurons in the ventral tegmental area (part of the mesolimbic reward system) by reducing
potassium currents that create afterhyperpolarizations. The other involves GABA; ethanol at
relatively low doses seems to affect GABAA receptors on GABAergic neurons, disinhibiting
dopaminergic reward pathways (Pierce & Kumaresan, 2008). However, ethanol also acts on
GABAA receptors present on GABAergic neurons; this leads to the hypothesis that receptors on
dopaminergic neurons are more sensitive to ethanol’s effects than those on GABAergic
counterparts, which is supported by electrophysiological experiments (Pierce & Kumaresean,
2008) (Grace & Bunney, 1979). This hypothesis also conveniently explains why alcohol
produces central nervous system stimulation at lower dosages and depression at higher dosages.
This investigation attempted to determine the extent to which GABA has a role in alcohol
addiction in C. elegans, a convenient model organism. It was initially hypothesized that a C.
elegans mutant strain (CB156) that does not produce GABA would develop an enhanced
preference to ethanol in the environment as compared to wild-type worms. Adult C. elegans
hermaphrodites were exposed to an environment containing ethanol, then transferred to an
environment where they could choose to move towards or away from ethanol disks. Preference
indices were calculated to quantify the degree to which each experimental group preferred
ethanol-containing environments. The results showed that GABA-deficiency and enhanced
ethanol preference were not necessarily correlated, and that there was no statistically significant
difference in chemotaxis towards ethanol between wild-type and GABA-deficient nematodes.
This indicates that GABA may not play as important a role in ethanol preference development as
was originally hypothesized.
Evan Hale - Sample Research Abstract
References
Falk, D., Yi, H.-Y., & Hiller-Sturmhöfel, S. (2008). An epidemiologic analysis of co-occurring
alcohol and drug use and disorders: Findings from the National Epidemiologic Survey of
Alcohol and Related Conditions (NESARC). Alcohol Research & Health, 31(2),100–110.
Filip, M., & Frankowska, M. (2008). GABAB receptors in drug addiction. Pharmacological
Reports, 60, 755-770.
Grace, A.A., & Bunney, B.S. (1979). Paradoxical GABA excitation of nigral dopaminergic cells:
Indirect mediation through reticulata inhibitory neurons. Eur. J. Pharmacol, 59, 211–218.
Pierce, R.C., & Kumaresan, V. (2006). The mesolimbic dopamine system: The final common
pathway for the reinforcing effect of drugs of abuse? Neuroscience and Biobehavioral
Reviews, 30, 215-238.
Purves, D., Augustine, G.J., Fitzpatrick, D., Katz, L.C., LaMantia, A, McNamara, J.O., &
Williams, S.M. (2001). Neuroscience (2nd ed.). Sunderland, MA: Sinaeur Associates.
Riddle, D.L., Blumenthal, T., Meyer, B.J., & Priess, J.R. (Eds.). (1997). C. elegans II (2nd ed.).
Cold Spring Harbor, NY: Cold Spring Harbor Press.