Dworkin S I, Mirkis S, Smith J E
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Psychopharmacology (Berl). 1995 Feb;117(3):262-6. doi: 10.1007/BF02246100.
The drug self-administration paradigm is routinely used to assess the abuse liability of psychoactive compounds. Investigations of the behavioral effects of drug use, however, often involve the response-independent (experiment-delivered) administration of the compound. It is frequently assumed that response-independent presentation of a compound has the same effects as response dependent deliveries. The present study examined directly the effects of response-dependent (self-administered) versus response-independent (experimenter-delivered) administration of cocaine on food intake and lethality. Littermate triads were exposed to either cocaine (0.33 mg/infusion) or saline using a yoked-box procedure. One member of the triad self-administered the drug under a fixed-ratio 2 schedule. The other two rats received response-independent infusions of either cocaine or saline. Groups of triads were exposed to two different cocaine access conditions. Daily sessions were terminated after 6 h for one group and after the delivery of 80 infusions for the other. The mean number of infusions delivered each session was 47 (+/- 12) and 70 (+/- 11), respectively, for the 6-h and 80-infusion condition. Under the 80-infusion condition, response-independent infusions of cocaine resulted in a significantly higher rate of mortality compared to littermates self-administering identical amounts of the drug. A fewer number of deaths occurred under 6-h condition; however, only rats exposed to response-independent infusions died under both access conditions. These data indicate that the presence or absence of response dependency can profoundly alter the lethal effects of cocaine.
药物自我给药范式通常用于评估精神活性化合物的滥用可能性。然而，对药物使用行为影响的研究往往涉及化合物的非反应依赖性（实验给予）给药。人们常常认为，化合物的非反应依赖性呈现与反应依赖性给药具有相同的效果。本研究直接考察了可卡因的反应依赖性（自我给药）与非反应依赖性（实验者给予）给药对食物摄入量和致死率的影响。同窝出生的三只一组的大鼠采用配对箱程序，分别给予可卡因（0.33毫克/注射）或生理盐水。每组中的一只大鼠在固定比率为2的给药方案下自我给药。另外两只大鼠接受非反应依赖性的可卡因或生理盐水注射。每组大鼠被置于两种不同的可卡因给药条件下。一组大鼠在6小时后结束每日实验，另一组大鼠在注射80次后结束实验。在6小时和80次注射条件下，每次实验平均注射次数分别为47（±12）次和70（±11）次。在80次注射条件下，与自我给药相同剂量药物的同窝大鼠相比，非反应依赖性注射可卡因导致的死亡率显著更高。在6小时条件下死亡的大鼠较少；然而，在两种给药条件下，只有接受非反应依赖性注射的大鼠死亡。这些数据表明，反应依赖性的存在与否可深刻改变可卡因的致死作用。
