Pelloux Yann, Everitt Barry J, Dickinson Anthony
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
Psychopharmacology (Berl). 2007 Sep;194(1):127-37. doi: 10.1007/s00213-007-0805-0. Epub 2007 May 21.
Abstinence from drug occurs in human addicts for several reasons, including the avoidance of adverse consequences.
To explore a model of drug use in the face of adverse consequences in rats through intermittent punishment of drug seeking and to investigate whether the ability to withhold seeking responses depends upon the duration of drug history.
Rats were trained under a seeking-taking chained schedule with sucrose or cocaine as reinforcer. Pressing the seeking lever gave access to the taking lever, and a single press on this lever delivered the reinforcer after which the seeking-taking chain recycled. During punishment, half of the seeking links terminated with a mild foot shock without access to the taking link.
After a moderate history of reinforcement, punishment of the terminal response in the seeking link suppressed both sucrose- and cocaine-seeking responses. By contrast, rats with an extended cocaine history were more resistant to punishment than those with a moderate cocaine history. This enhanced resistance to punishment was due to a sub-group of rats that showed minimal or no suppression of drug seeking. No differences in suppression of sucrose seeking were observed in animals with moderate versus extended sucrose histories.
These results suggest that an extended drug self-administration history decreases the ability of vulnerable rats to suppress their drug seeking.
人类成瘾者会出于多种原因戒毒,包括避免不良后果。
通过间歇性惩罚觅药行为来探索大鼠在面对不良后果时的药物使用模式,并研究抑制觅药反应的能力是否取决于用药史的时长。
大鼠在以蔗糖或可卡因作为强化物的觅药 - 取药连锁程序下接受训练。按压觅药杠杆可进入取药杠杆,单次按压该杠杆会提供强化物,之后觅药 - 取药循环重新开始。在惩罚阶段,一半的觅药环节以轻度足部电击结束,且无法进入取药环节。
在经历适度强化历史后,对觅药环节中的终端反应进行惩罚会抑制蔗糖和可卡因的觅药反应。相比之下,有较长可卡因用药史的大鼠比有适度可卡因用药史的大鼠对惩罚更具抵抗力。这种增强的惩罚抵抗力归因于一组表现出极少或没有觅药抑制的大鼠。在有适度蔗糖用药史和较长蔗糖用药史的动物中,未观察到蔗糖觅药抑制的差异。
这些结果表明,延长的药物自我给药史会降低易成瘾大鼠抑制其觅药行为的能力。