Family History of Alcoholism Is Associated With Lower 5-HT2A Receptor Binding in the Prefrontal Cortex Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 30 Jan 2008
5-Hydroxytryptophan (5-HT2A) receptor involvement in alcoholism is suggested by less 5-HT2A binding in alcohol preferring rats, association of a 5-HT2A receptor gene polymorphism with alcohol dependence and reduced alcohol intake with 5-HT2A antagonists.
We sought to determine postmortem whether 5-HT2A receptors are altered in the prefrontal cortex (PFC) of alcoholics.
5-HT2A binding decreased with age [Brodmann areas (BA) 9, 46 gyrus; r = −0.381, −0.334, p <>n = 23) had less 5-HT2A binding throughout PFC than subjects without (n = 21) a family history of alcoholism (p <>2A receptor binding in alcoholics without a family history of alcoholism (n = 7) did not differ from controls without a family history of alcoholism (n = 14). There was no association between alcoholism or alcohol rating and genotype. There was an association between genotype and the total amount of 3H-ketanserin binding in BA46 with the TT genotype having more binding (TT>TC≈CC).
Lower 5-HT2A receptor binding in the PFC of cases with a family history of alcoholism suggests a genetic predisposition to alcoholism. Alcohol abuse by itself did not have a significant effect on PFC 5-HT2A binding and as 5-HT2A binding in alcoholics is not different from controls and antagonists may be therapeutic, fewer receptors may result in downstream developmental effects on the brain resulting in a predisposition to alcoholism
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