Twenty-two 50-month-old rhesus monkeys were prodded concurrent free access to an aspartamesweetened 7% ethanol solution and an aspartame-sweetened vehicle before, during, and after social separation. Subjects had been reared for their first 6 months of life either without access to adults but with constant access to age mates (peer reared), a condition producing reduced exploration and increased fear-related behaviors, or as controls with their mothers; thereafter, all subjects received identical treatment. During home-cage periods, for 1 hr each day, 4 days a week, when the ethanol solution and vehicle were freely available, peerreared subjects consumed significantly more alcohol than mother-reared subjects. When stress was increased via social separation, mother-reared animals increased their alcohol consumption to a level nearly as high as that of peer-reared monkeys. Average individual differences in alcohol consumption were markedly stable over time. In addition, there were strong positive correlations between alcohol consumption and distress behaviors. Biological indices of increased stress, such as plasma cortisol and corticotropin, were higher in peerreared subjects. Within the peer-and mother-reared groups, these indices were positively correlated with alcohol consumption. The results suggest that early rearing experiences that predispose monkeys to increased fear-related behaviors produce excessive alcohol consumption under normal living conditions. Furthermore, a major challenge such as social separation increases alcohol consumption to levels producing intoxication even in monkeys not particularly vulnerable to stress.
The function of brain serotonin-2C (5-HT2C) receptors, including behavioral and neurochemical responses to 5-HT2C agonist challenge, has been suggested to be abnormal in individuals with neuropsychiatric disorders. Thus, it is important to identify polymorphisms and functional variants within this gene. Using SSCP analysis, we identified a Cys23-Ser23 substitution (designated 5-HT2Ccys and 5-HT2Cser) in the first hydrophobic region of the human 5-HT2C receptor. Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT2Cser and 5-HT2Ccys, respectively. DNAs from informative CEPH families were typed for this polymorphism and analyzed with respect to 20 linked markers on the X chromosome. Linkage analysis placed the 5-HT2C receptor gene (HTR2C) on Xq24. To evaluate whether this amino acid substitution causes a variant function of this receptor, recombinant human 5-HT2Ccys and 5-HT2Cser receptors were expressed in Xenopus oocytes and tested for responses to 5-HT using electrophysiological techniques. Concentration-response curves for 5-HT were not significantly different in oocytes expressing either form of the receptor, suggesting that the 5-HT2Ccys and 5-HT2Cser receptor proteins may not differ in their responses to serotonin under baseline physiological conditions.
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