Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats
Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats
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DOI：
10.1007/s002130050937
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发表时间：
1999-04-01
影响因子：
3.4
通讯作者：
Carroll, ME
中科院分区：
文献类型：
--
作者：
Campbell, UC;Lac, ST;Carroll, ME
基本原理：最近的研究表明，GABA（B）受体激动剂巴氯芬可能是一种有用的药物治疗可卡因滥用。目的：进一步研究巴氯芬对可卡因强化大鼠行为的维持和恢复作用。研究方法：训练两组大鼠在固定比率1时间表下在每日7小时的会议期间自我给予IV可卡因（每次输注0.2或0.4 mg/kg）。大鼠预处理与巴氯芬（1.25，2.5或5毫克/公斤IF）或生理盐水之前，会议连续5天。另一组大鼠接受训练，在每天7小时的前2小时内自我静脉注射可卡因（每次输注0.4 mg/kg）。在剩余的5小时内，用生理盐水代替考马斯亮蓝。一旦行为在7小时内稳定，在第4小时之前给予生理盐水（IV）、可卡因（3.2 mg/kg IV）或巴氯芬（1.25或2.5 mg/kg IF）的引发注射。在注射可卡因之前，还注射巴氯芬（1.25或2.5 mg/kg IF）或盐水。结果如下：在5天治疗期间，两个维持组（0.2和0.4 mg/kg）中，两个较高剂量的巴氯芬（2.5和5 mg/kg）预治疗减少了可卡因输注次数。巴氯芬对低剂量可卡因维持的反应有更大的抑制作用。巴氯芬（1.25和2.5 mg/kg）或生理盐水的引发注射没有恢复反应。然而，这些相同剂量的巴氯芬剂量依赖性地减少了由可卡因引发注射产生的反应的恢复。结论：1）巴氯芬对可卡因自我给药维持的抑制作用的大小取决于维持剂量，2）巴氯芬可能有助于预防可卡因寻求行为的恢复，3）与维持相比，反应的恢复对巴氯芬的抑制作用更敏感。
Rationale: Recent studies suggest that the GABA(B) receptor agonist, baclofen, may be a useful pharmacotherapy for cocaine abuse. Objectives: To investigate further the effects of baclofen on maintenance and reinstatement of cocaine-reinforced behavior in rats. Methods: Two groups of rats were trained to self-administer IV cocaine (0.2 or 0.4 mg/kg per infusion) during daily 7-h sessions under a fixed-ratio 1 schedule. Rats were pretreated with baclofen (1.25, 2.5 or 5 mg/kg IF) or saline before the session for 5 consecutive days. An additional group of rats was trained to self-administer IV cocaine (0.4 mg/kg per infusion) during the first 2 h of daily 7-h sessions. Cocaine was replaced by saline for the remaining 5 h of the session. Once behavior had stabilized over the 7-h period, priming injections of saline (IV), cocaine (3.2 mg/kg IV) or baclofen (1.25 or 2.5 mg/kg IF) were administered prior to hour 4. Injections of baclofen (1.25 or 2.5 mg/kg IF) or saline were also given before priming injections of cocaine. Results: Pre treatment with the two higher doses of baclofen (2.5 and 5 mg/kg) decreased the number of cocaine infusions in both maintenance groups (0.2 and 0.4 mg/kg) over the 5- day treatment period. Baclofen had a greater suppressant effect on responding maintained by the lower dose of cocaine. Priming injections of baclofen (1.25 and 2.5 mg/kg) or saline did not reinstate responding. However, these same doses of baclofen dose-dependently reduced the reinstatement of responding produced by priming injections of cocaine. Conclusions: 1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.