Family History of Alcoholism Is Associated With Lower 5-HT 2A Receptor Binding in the Prefrontal Cortex (original) (raw)
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Alcoholism: Clinical and Experimental Research, 2008
Background: 5-Hydroxytryptophan (5-HT 2A) receptor involvement in alcoholism is suggested by less 5-HT 2A binding in alcohol preferring rats, association of a 5-HT 2A receptor gene polymorphism with alcohol dependence and reduced alcohol intake with 5-HT 2A antagonists. We sought to determine postmortem whether 5-HT 2A receptors are altered in the prefrontal cortex (PFC) of alcoholics. Methods: Brain tissue from 25 alcoholics and 19 controls was collected at autopsy. Diagnosis of DSM-IV alcoholism ⁄ abuse and other psychiatric disorders and the determination of family history of alcoholism were made by psychological autopsy. Specific binding to 5-HT 2A (3 H-ketanserin) receptors in the PFC was measured by quantitative autoradiography. Results: 5-HT 2A binding decreased with age [Brodmann areas (BA) 9, 46 gyrus; r =)0.381,)0.334, p < 0.05]. No differences in receptor binding between alcoholics and controls were detected in the gyrus or sulcus of any PFC area examined. Cases (controls or alcoholics) with a family history of alcoholism (n = 23) had less 5-HT 2A binding throughout PFC than subjects without (n = 21) a family history of alcoholism (p < 0.05). 5-HT 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 3 H-ketanserin binding in BA46 with the TT genotype having more binding (TT>TCCC). Conclusions: Lower 5-HT 2A 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-HT 2A binding and as 5-HT 2A 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.
Alcohol and Alcoholism, 2008
The Cloninger type 1 alcoholics are prone to anxiety, and in many cases patients have begun to use alcohol in order to relieve their anxiety. We have previously reported a decrease of the serotonin transporter density in the perigenual anterior cingulate cortex (pACC) in type 1 alcoholics. The 5-HT(1A) receptors are the binding sites for anxiolytic drug buspirone. We aimed to investigate the alteration in the density of 5-HT(1A) receptors, that may also alter the effect of serotonin in the pACC in alcoholics. The density of the serotonin receptor 5-HT(1A) among Cloninger type 1 and 2 alcoholics (nine and eight subjects, respectively) and 10 control subjects were determined by postmortem whole-hemisphere autoradiography with WAY-100635. Substantially sparser 5-HT(1A) (by -31%, P = 0.010) density was observed in the pACC of alcoholic subjects in relation to non-alcoholic comparison subjects. In a secondary analysis for the difference between the alcoholic subtypes and controls, the 5-HT(1A) density was decreased significantly by -32% (P = 0.015) in the upper level of pACC in type 1 alcoholics. The detected decrease of 5-HT(1A) receptor density on the pACC suggests further that the serotoninergic system is defected in the so-called affect region, especially in the type 1 alcoholics.
Whole-hemisphere autoradiography of 5-HT1B receptor densities in postmortem alcoholic brains
2012
The 5-HT 1B receptor has been associated with alcohol dependence, impulsive or alcohol-related aggressive behavior, and anxiety. The aim of this study was to determine whether or not the 5-HT 1B receptor density differs in brain samples from anxiety-prone Cloninger type 1 alcoholics and socially hostile, predominantly male, type 2 alcoholics, and controls. Whole-hemispheric 5-HT 1B receptor density was measured in eight regions of postmortem brains from 17 alcoholics and 10 nonalcoholic controls by autoradiography with tritiated GR-125743 and unlabeled ketanserin to prevent 5-HT 1D binding. The 5-HT 1B receptor density was not altered significantly in any of the studied regions. However, some correlations were observed in types 1 and 2 alcoholics only. The 5-HT 1B receptor density decreased with age in type 1 alcoholics only. There was a significant positive correlation between 5-HT 1B receptor and serotonin transporter densities in the head of caudate of type 1 alcoholics only. There was a significant positive correlation between 5-HT 1B receptor density and dopaminergic terminal density, as estimated by vesicular monoamine transporter 2 measurement in the nucleus accumbens of type 2 alcoholics only. There were no significant correlations between 5-HT 1B receptor and dopamine transporter or dopamine D2/D3 receptor densities in any of the subject groups. In conclusion, these results do not indicate primary changes in 5-HT 1B receptor densities among these alcoholics, although the data must be considered as preliminary.
Reappraisal of the serotonin 5-HT1B receptor gene in alcoholism: of mice and men
Brain Research Bulletin, 2002
Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT 1B type can play a modulatory role in alcohol consumption in both human and rodents, the 5-HT 1B receptor gene is considered as a candidate gene for alcohol dependence. However, contradictory results have been reported as a positive association between alcohol dependence, and either the 861C or the 861G allele of the G861C polymorphism of the 5-HT 1B receptor gene can be found in the literature. Further investigations in a population of 136 male alcoholics compared with 72 male control subjects demonstrated that none of these alleles was actually associated with alcohol dependence. In addition, in contrast with previous results of the literature, ethanol intake under free choice conditions (i.e., ethanol solution vs. water) was found to be similar in 5-HT 1B ؊/؊ knock mice and paired wild-type controls. The 5-HT 1B receptor gene may thus not be a key component in the genetic background underlying alcohol dependence in human and alcohol preference in rodents, although these results should be considered as preliminary according to the small size of our sample.
Neurotransmitters in alcoholism: A review of neurobiological and genetic studies
2014
Recent advances in the study of alcoholism have thrown light on the involvement of various neurotransmitters in the phenomenon of alcohol addiction. Various neurotransmitters have been implicated in alcohol addiction due to their imbalance in the brain, which could be either due to their excess activity or inhibition. This review paper aims to consolidate and to summarize some of the recent papers which have been published in this regard. The review paper will give an overview of the neurobiology of alcohol addiction, followed by detailed reviews of some of the recent papers published in the context of the genetics of alcohol addiction. Furthermore, the author hopes that the present text will be found useful to novices and experts alike in the field of neurotransmitters in alcoholism.