ROLE OF OPIOID RECEPTOR SUBTYPES IN THE SUBJECTIVE EFFECTS OF ETHANOL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。阿片受体被认为对乙醇的强化和复发诱导作用有贡献。然而，这些受体在乙醇的主观效应中的作用尚未得到很好的理解。本研究的目的是利用药物鉴别程序评估μ和δ阿片受体对乙醇主观效应的贡献。松鼠猴被训练在固定比例的食物递送时间表下区分乙醇和生理盐水。在测试条件下，乙醇产生了剂量依赖性的药物杠杆反应增加，达到平均最大值大于80%。在使用低剂量的受体选择性拮抗剂纳曲酮以及低剂量的受体选择性拮抗剂纳曲多后，乙醇的主观效应减弱。受体激动剂吗啡和受体激动剂snc80既没有取代也没有增强乙醇的主观作用。然而，作为预处理，吗啡和snc80都减弱了乙醇的主观效应，并加剧了乙醇的降速效应。虽然不能排除吗啡和SNC 80对乙醇主观效应的药理拮抗作用，但更可能的是乙醇效应减弱是由于阿片激动剂对乙醇刺激的知觉掩膜。然而，纳曲酮和纳曲多阻断乙醇主观效应的能力可能反映了它们减弱乙醇诱导的内源性阿片样物质增加的能力，因为乙醇刺激的减弱并不伴随着反应率的抑制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Opioid receptors are thought to contribute to the reinforcing and relapse-inducing effects of ethanol. However, the role of these receptors in the subjective effects of ethanol is not yet well understood. The purpose of this study was to evaluate the contribution of mu and delta opioid receptors to the subjective effects of ethanol using drug discrimination procedures. Squirrel monkeys were trained to discriminate ethanol from saline under a fixed-ratio schedule of food delivery. Under test conditions, ethanol engendered a dose-dependent increase in drug-lever responding, reaching an average maximum of greater than 80 per cent. The subjective effects of ethanol were attenuated following administration of low, mu receptor-selective doses of the antagonist naltrexone, as well as after administration of low, delta receptor-selective doses of the antagonist naltrindole. The mu receptor agonist morphine and the delta receptor agonist SNC 80 neither substituted for nor enhanced the subjective effects of ethanol. When administered as pretreatments, however, both morphine and SNC 80 attenuated the subjective effects of ethanol and exacerbated ethanol's rate decreasing effects. Although the possibility of pharmacological antagonism of the subjective effects of ethanol by morphine and SNC 80 cannot be ruled out, a more likely alternative is that the diminished effects of ethanol were due to perceptual masking of the ethanol stimulus by the opioid agonists. The ability of naltrexone and naltrindole to block the subjective effects of ethanol, however, likely reflects their capacity to attenuate ethanol-induced increases in endogenous opioids because attenuation of the ethanol stimulus was not accompanied by suppression of response rate.