Knackstedt Lori A, Kalivas Peter W
Department of Neurosciences, Medical University of South Carolina, 173 Ashley Ave, BSB Suite 403, Charleston, SC 29425, USA.
J Pharmacol Exp Ther. 2007 Sep;322(3):1103-9. doi: 10.1124/jpet.107.122861. Epub 2007 Jun 29.
Cocaine addicts increase the frequency and amount of drug use over time. This characteristic has been modeled by escalating drug intake in rats that were given extended access to cocaine. However, it remains unclear whether the behavior of escalating drug intake or simply increased drug dose is the relevant aspect of this model. The present study investigated whether the phenomenon of escalated drug-taking enhances cocaine-induced sensitization and reinstatement. Rats were trained to self-administer cocaine during daily 1-h sessions for 7 days. A short-access (ShA) group continued to receive 1-h sessions for 10 days while a group of rats was switched to 6 h of drug access, long-access (ShA-LgA) group, for 10 days. In addition, a long-access only (LgA-only) group was added that was not pretrained but was only given extended access for 10 days. ShA subjects maintained stable drug intake; ShA-LgA subjects escalated intake while LgA-only subjects decreased drug intake. All groups displayed an inverted-U shaped cocaine dose-response curve in both the sensitization and reinstatement tests. There was no difference in the expression of behavioral sensitization between groups. Whereas both long-access groups showed reinstatement at more doses of cocaine than the ShA group, the presence of escalation did not affect reinstatement. These results indicate that extended access to cocaine self-administration produces behavioral differences relative to traditional short-access animals in reinstatement, but not sensitization. Furthermore, the differences in reinstatement are predicted more by length of cocaine access than by escalation of drug intake.
随着时间的推移，可卡因成瘾者会增加吸毒的频率和剂量。这一特性已通过让大鼠长时间接触可卡因并逐渐增加药物摄入量来进行模拟。然而，目前尚不清楚药物摄入量增加的行为还是仅仅是药物剂量的增加是该模型的相关方面。本研究调查了药物摄入增加的现象是否会增强可卡因诱导的敏化和复吸。大鼠在每天1小时的时间段内接受7天的可卡因自我给药训练。一个短接触组（ShA）在接下来的10天里继续每天接受1小时的药物接触，而另一组大鼠则改为6小时的药物接触，即长接触组（ShA-LgA），持续10天。此外，还增加了一个仅长接触组（LgA-only），该组没有预先训练，只是给予10天的延长接触时间。ShA组的大鼠保持稳定的药物摄入量；ShA-LgA组的大鼠摄入量增加，而LgA-only组的大鼠药物摄入量减少。在敏化和复吸测试中，所有组均呈现倒U形的可卡因剂量反应曲线。各组之间行为敏化的表现没有差异。虽然两个长接触组在更多可卡因剂量下都出现了复吸，而ShA组则没有，但摄入量的增加并没有影响复吸。这些结果表明，相对于传统的短接触动物，延长可卡因自我给药的接触时间在复吸方面产生了行为差异，但在敏化方面没有。此外，复吸的差异更多地是由可卡因接触时间的长短预测的，而不是药物摄入量的增加。
