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Chunk #5 — Human studies

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The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks.
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The positive reinforcing effects of alcohol are mediated through the corticomesolimbic dopaminergic reward pathway, which extends from the ventral tegmental area to the nucleus accumbens and is modulated by a wide range of neurotransmitters. This pathway is indirectly activated by alcohol through the release of other neurotransmitters, including acetylcholine, dopamine, glutamate, gamma-aminobutyric acid (GABA), opioids and serotonin. Several candidate genes in neurotransmitter pathways associated with the ventral tegmental area and nucleus accumbens have been associated with alcohol dependence, including the genes encoding cholinergic receptor, muscarinic 2 (CHRM2) [12]; cholinergic receptor, nicotinic, alpha 5 (CHRNA5) [13]; catechol-O-methyltransferase (COMT) [9]; GABA A receptor, alpha 2 (GABRA2) [14]; glutamate receptor, metabotropic 8 (GRM8) [15]; solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (5-HTT) [16]; nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (NFKB1) [17]; monoamine oxidase A (MAOA) [18]; neuropeptide Y receptor Y2 (NPY2R) [19]; opioid receptor, kappa 1 (OPRK1) [20]; opioid receptor, mu 1 (OPRM1) [21]; prodynorphin (PDYN) [20]; and tachykinin receptor 3 (TACR3) [22].