Lecture 6

Lecture 6 - Lecture 6- More on GABA + Genetics of...

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Lecture 6- More on GABA + Genetics of Alcoholism KEY CONCEPTS GABAA and alcohol-related behaviour (animal studies) twin and adoptee studies of alcoholism COGA – collaborative study on the genetics of alcoholism in the US potential genetic markers and candidate genes
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GABA A subunits and behaviour GABA A antagonists (i.e. SR95531, picrotoxin, bicuculline) have been shown to reduce bar-pressing for oral alcohol in rats specific subunits of the GABA A receptor have been associated with alcohol effects in animal studies – particularly the α1, α6, δ (mice lacking the α1 subunit (KO mice) showed decreased ethanol consumption (Blednov et al. 2003)) In animal studies, decreased α1 + increased α4, α5 and α6 mRNA following chronic consumption. α4β2γ2 receptors appear to be less sensitive to alcohol resulting in tolerance (has not been shown in humans)
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GABA A antagonists (i.e. SR95531, picrotoxin, bicuculline) have been shown to reduce oral alcohol in rats Nowak et al., microinjected antagonists into the VTA, observing specific effects on alcohol intake
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Picrotoxin
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expression of different subunits in the rat brain GABA receptor subunit composition varies over different regions implication is that alcohol sensitivity will be different, across various subunits and brain regions
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α4β3γ2 and α4β3δ receptors differ in terms of alcohol sensitivity the δ subunit appears to produce an alcohol sensitive GABA receptor, and is part of the binding site for Ro15-4513 this compound is an alcohol antagonist, that blocks many of alcohol’s actions (but not all)
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Are alcohol and drug dependence inherited?
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Family History of Alcoholism
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Family History Positive (FHP) Substance Abusers Earlier onset (<15 age of onset of alcohol abuse associated with increased smoking + drug use) Higher prevalence of ASPD More severe (e.g. physical dependence) Lower educational and occupational achievement (deficits in ECF such as problem solving,
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This note was uploaded on 04/26/2011 for the course PSYT 301 taught by Professor Kathryngill during the Winter '11 term at McGill.

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Lecture 6 - Lecture 6- More on GABA + Genetics of...

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