慢性 d-苯丙胺给药对恒河猴可卡因强化效力的影响。
Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys.
机构信息
Department of Physiology and Pharmacology, Center for the Neurobiology of Addiction Treatments (CNAT), Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.
出版信息
Psychopharmacology (Berl). 2010 May;209(4):375-82. doi: 10.1007/s00213-010-1807-x. Epub 2010 Mar 9.
RATIONALE
Agonist medications have been proven effective in treating opioid and nicotine dependence; results from clinical studies suggest that the indirect dopamine agonist d-amphetamine may reduce cocaine abuse. In preclinical studies, chronic d-amphetamine treatment decreased ongoing cocaine self-administration.
OBJECTIVES
The present study extended previous results by determining effects of chronic d-amphetamine treatment on the reinforcing strength of cocaine under conditions in which access to cocaine was suspended during d-amphetamine treatment.
METHODS
Daily operant conditioning sessions consisted of morning access to food pellets delivered under a 50-response fixed-ratio schedule and evening access to cocaine (0.005-0.48 mg/kg per injection, i.v.) under a progressive-ratio schedule. After responding maintained by 0.045 mg/kg per injection cocaine stabilized, self-administration sessions were suspended and d-amphetamine (0.01-0.1 mg/kg per hr, i.v.) was administered continuously for 5 days. On the following day, d-amphetamine treatment was discontinued and daily self-administration sessions resumed.
RESULTS
Following termination of d-amphetamine treatment, food- and cocaine-maintained responding was decreased in a dose-related manner. Decreases in the reinforcing strength of cocaine were larger and lasted longer than effects on food reinforcement. However, cocaine self-administration was unaltered if 6 days elapsed between discontinuation of d-amphetamine treatment and the next cocaine self-administration session.
CONCLUSIONS
The necessity of a self-administration session in the presence of d-amphetamine suggests that the protracted decrease in cocaine self-administration may be a manifestation of behavioral tolerance. Regarding treatment of cocaine dependence, data suggest that prolonged d-amphetamine treatment may be necessary to produce a sustained reduction in the reinforcing effects of cocaine.
原理
激动剂药物已被证明可有效治疗阿片类药物和尼古丁依赖；临床研究结果表明，间接多巴胺激动剂 d-苯丙胺可能减少可卡因滥用。在临床前研究中，慢性 d-苯丙胺治疗减少了可卡因的持续自我给药。
目的
本研究通过确定慢性 d-苯丙胺治疗对可卡因强化作用的影响，扩展了以前的结果，即在 d-苯丙胺治疗期间暂停可卡因使用的情况下。
方法
每日操作性条件作用会话由早晨进食丸（根据 50 次固定比例计划交付）和晚上可卡因（0.005-0.48 mg/kg 每剂，静脉内）（根据渐进比例计划）组成。当 0.045mg/kg 每剂可卡因维持的反应稳定后，自我给药会话暂停，d-苯丙胺（0.01-0.1mg/kg 每小时，静脉内）连续给药 5 天。在接下来的一天，停止 d-苯丙胺治疗，每天恢复自我给药会话。
结果
在 d-苯丙胺治疗终止后，食物和可卡因维持的反应以剂量相关的方式减少。可卡因强化作用的降低比食物强化作用的降低更大且持续时间更长。然而，如果在停止 d-苯丙胺治疗和下一次可卡因自我给药会话之间间隔 6 天，则可卡因自我给药不会改变。
结论
在 d-苯丙胺存在的情况下自我给药会话的必要性表明，可卡因自我给药的长期减少可能是行为耐受性的表现。关于可卡因依赖的治疗，数据表明，可能需要延长 d-苯丙胺治疗才能产生可卡因强化作用的持续减少。
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