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在恒河猴的同时进行的渐进比率程序下,纳曲酮预处理降低了乙醇和糖精的强化效力,但不影响苯环己哌啶或食物的强化效力。

Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys.

作者信息

Rodefer J S, Campbell U C, Cosgrove K P, Carroll M E

机构信息

Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA.

出版信息

Psychopharmacology (Berl). 1999 Feb;141(4):436-46. doi: 10.1007/s002130050854.

Abstract

The purpose of this experiment was to determine whether attenuation of ethanol consumption by naltrexone is the result of selective changes in the reinforcing effectiveness of drug and non-drug reinforcers. A range of naltrexone doses (0.1-1.0 mg/kg) was administered for 5 days, and the effects on the reinforcing effects of orally delivered 8% (w/v) ethanol, 0.25 mg/ml phencyclidine (PCP), 0.03% (w/v) saccharin and food were studied in eight rhesus monkeys. Food and liquids were available under independent and concurrent progressive-ratio (PR) schedules (ratio range 8-4096) during daily 3-h sessions. Ethanol-maintained responding was attenuated by 0.3 and 1.0 mg/kg doses of naltrexone, while saccharin-maintained responding was decreased at the 1.0 mg/kg dose. Furthermore, there was a significant linear trend that consumption of available ethanol and saccharin was attenuated dose-dependently by naltrexone. Following 5 days of naltrexone pretreatment, ethanol- and saccharin-maintained responding immediately returned to or exceeded baseline levels. Food- and PCP-maintained responding and intake were not significantly affected by any of the naltrexone doses examined. The decreased break point (BP) values for ethanol and saccharin suggest that their reinforcing effects are mediated through opioid reinforcement mechanisms. The lack of naltrexone attenuation of PCP- and food-maintained responding suggests that these reinforcers: 1) are not sensitive to naltrexone antagonism at the doses examined, 2) are mediated by non-opioid reinforcement mechanisms, and/or 3) have less intrinsic palatability.

摘要

本实验的目的是确定纳曲酮减少乙醇摄入量是否是药物和非药物强化物强化效果发生选择性变化的结果。给予一系列纳曲酮剂量(0.1 - 1.0毫克/千克),持续5天,并在8只恒河猴中研究其对口服8%(w/v)乙醇、0.25毫克/毫升苯环己哌啶(PCP)、0.03%(w/v)糖精和食物强化效果的影响。在每天3小时的实验时段内,食物和液体可通过独立和同时进行的累进比率(PR)程序(比率范围8 - 4096)获取。0.3和1.0毫克/千克剂量的纳曲酮可减弱乙醇维持的反应,而1.0毫克/千克剂量的纳曲酮可降低糖精维持的反应。此外,存在显著的线性趋势,即纳曲酮剂量依赖性地减弱可获取乙醇和糖精的摄入量。在纳曲酮预处理5天后,乙醇和糖精维持的反应立即恢复到或超过基线水平。食物和PCP维持的反应及摄入量未受到所检测的任何纳曲酮剂量的显著影响。乙醇和糖精的断点(BP)值降低表明它们的强化效果是通过阿片类强化机制介导的。纳曲酮对PCP和食物维持的反应没有减弱作用,这表明这些强化物:1)在所检测的剂量下对纳曲酮拮抗不敏感,2)由非阿片类强化机制介导,和/或3)内在适口性较低。

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