Effects of opiate antagonist treatment on the alcohol deprivation effect in long-term ethanol-experienced rats
Effects of opiate antagonist treatment on the alcohol deprivation effect in long-term ethanol-experienced rats
复制标题
DOI：
10.1007/s002130051069
复制
发表时间：
1999-08-01
影响因子：
3.4
通讯作者：
Spanagel, R
中科院分区：
文献类型：
--
作者：
Hölter, SM;Spanagel, R
理由：阿片拮抗剂是治疗酒精依赖的有前途的药物治疗剂，可减少戒酒者的渴望和复发率。然而，临床前研究结果表明，它们还可以增加强烈喜欢乙醇的动物的乙醇消耗和偏好，具体取决于剂量和治疗方案。目的：本研究探讨了慢性、间歇性和急性阿片拮抗剂治疗对长期经历乙醇的大鼠（一种渴望和复发的动物模型）的酒精剥夺效应（ADE）的影响。方法：长期接触乙醇的大鼠要么植入微型渗透泵，每小时输送 0、0.5 或 1 mg/kg 纳洛酮（长期治疗），要么接受间歇性纳曲酮注射（每天 2x5 mg/kg SC）。在四瓶家用笼饮模式中研究了慢性和间歇性治疗对 ADE 的影响。在第二个实验中。长期使用乙醇的大鼠在操作性乙醇自我给药模式中接受训练，在基础饮酒期间或 ADE 期间的 23 小时疗程前接受急性纳曲酮治疗（0、0.1、1 或 10 mg/kg SC）。结果：长期纳洛酮治疗增加了 ADE 期间对乙醇的偏好。间歇性纳曲酮治疗的剂量与慢性治疗的较低剂量相当，可适度减弱 ADE。急性纳曲酮治疗仅以最低剂量选择性地减少 ADE 期间和基础饮酒期间对乙醇的压力，而较高剂量也抑制了水的摄入。乙醇对 ADE 的特异性抑制作用是持久的。然而，就基础饮水而言，纳曲酮仅对水的压力有长期持续的减少作用。结论：低剂量的纳曲酮和间歇性治疗方案似乎对于维持高乙醇消费动机的个体乙醇摄入量的特定减少是必要的。这些发现与低剂量阿片拮抗剂会降低强化剂的奖励价值的观点是一致的。
Rationale: Opiate antagonists are promising pharmacotherapeutic agents for the treatment of alcohol dependence, reducing craving and relapse rates in weaned alcoholics. However, preclinical findings indicate that they can also increase ethanol consumption and preference in animals with a strong liking for ethanol, depending on the dose and treatment regimen. Objective: The present study examined the effects of chronic, intermittent and acute opiate antagonist treatment on the alcohol deprivation effect (ADE) in long-term ethanol-experienced rats, which is an animal model of craving and relapse. Methods: Long-term ethanol-experienced rats were either implanted with mini-osmotic pumps delivering 0, 0.5 or 1 mg/kg per hour naloxone (chronic treatment) or received intermittent naltrexone injections (2x5 mg/kg per day SC). Effects of chronic and intermittent treatment on the ADE were studied in a four-bottle home cage drinking paradigm. Ln a second experiment. long-term ethanol-experienced rats trained in an operant ethanol self-administration paradigm received acute naltrexone treatment (0, 0.1, 1 or 10 mg/kg SC) before a 23-h session either during basal drinking or during the ADE. Results: Chronic naloxone treatment increased ethanol preference during the ADE. Intermittent naltrexone treatment at a dose comparable to the lower dose of chronic treatment moderately attenuated the ADE. Acute naltrexone treatment selectively reduced lever pressing for ethanol both during the ADE and during basal drinking only at the lowest dose, whereas higher doses also suppressed water intake. The ethanol-specific suppressant effect on the ADE was long lasting. Concerning basal drinking, however, naltrexone had a long lasting reductive effect only on lever pressing for water. Conclusions: A low dose of naltrexone and an intermittent treatment regimen seem to be necessary to maintain a specific reduction in ethanol intake in individuals with a high motivation to consume ethanol. These findings are consistent with the notion that, at low doses, opiate antagonists reduce the reward value of reinforcers.