The overall goal of the proposed research is to assess the contribution of several receptor systems in mediating the interoceptive effects of a low and a moderate dose of ethanol in male and female non human primates. The interoceptive, or subjective, stimulus effects of ethanol can function as discriminative stimuli using drug discrimination procedures and can be used to evaluate possible receptor mechanisms implicated in mediating of these effects. Recent studies have suggested several receptor systems may mediate the discriminative stimulus effects of ethanol, including the GABA(A) receptor complex, the NMDA subtype of glutamate receptor complex, the 5-HT3 and 5-HT1 subtypes of serotonin receptors. However, very little information is available concerning the receptor systems that mediate the discriminative effects of ethanol in non human primates. The degree to which data gathered on the pharmacological basis of the ethanol cue in rodents extends to primates is important to evaluate, particularly considering at least one of the receptor systems (5-HT1B) suggested to mediate a component of the discriminative stimulus effects of ethanol shows species specificity. Therefore, it remains to be determined (1) whether the same receptor systems mediate the ethanol due in rodents and primates, and (2) the dose-dependent nature of the ethanol cue in primates. Furthermore, virtually all the data gathered on the discriminative stimulus effects of ethanol have been in male subjects. We propose to characterize the pharmacological basis of the discriminative effects of ethanol in both male and female of a species that has a estrous cycle similar to that of humans. To accomplish the goals of the proposed research, male and female cynomolgus monkeys (Macaca fascicularis) will be used.
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