Suto N, Austin J D, Tanabe L M, Kramer M K, Wright D A, Vezina P
Department of Psychology, The University of Chicago, Chicago, IL 60637, USA.
Neuropsychopharmacology. 2002 Dec;27(6):970-9. doi: 10.1016/S0893-133X(02)00379-2.
The effect of previous exposure to amphetamine (AMPH) in the ventral tegmental area (VTA) on the subsequent self-administration of cocaine was assessed. Rats in different groups were pre-exposed to three injections into the VTA of either saline (0.5 microl/side) or AMPH (2.5 microg/0.5 microl/side). Injections were given once every third day. Starting 7-10 days after the last pre-exposure injection, rats were trained to self-administer cocaine (0.3 mg/kg/infusion) under fixed ratio 1 and 2 (FR1 and FR2) schedules and then tested under a progressive ratio (PR) schedule of reinforcement for six consecutive days. No differences between groups were observed during self-administration training under the FR schedules of reinforcement. However, when tested under the PR schedule, VTA AMPH pre-exposed rats worked more and, as a result, obtained more infusions of cocaine than saline pre-exposed rats. Rats in a separate group pre-exposed to VTA AMPH but co-infused with the D(1)-like dopamine (DA) receptor antagonist SCH23390 (0.25 microg/0.5 microl/side) did not show enhanced cocaine self-administration. These rats, as well as others pre-exposed to VTA SCH23390 alone showed levels of cocaine self-administration similar to saline pre-exposed rats. Thus, in a manner paralleling the sensitization of AMPH-induced locomotion and nucleus accumbens DA overflow, previous exposure to AMPH in the VTA leads to enhanced intravenous self-administration of cocaine and activation of D(1) DA receptors in this site during pre-exposure is necessary for the production of this effect.
评估了之前腹侧被盖区（VTA）注射苯丙胺（AMPH）对后续可卡因自我给药的影响。不同组的大鼠分别接受三次向VTA注射生理盐水（0.5微升/侧）或AMPH（2.5微克/0.5微升/侧）的预处理。每隔三天注射一次。在最后一次预处理注射后7 - 10天开始，大鼠接受训练，在固定比率1和2（FR1和FR2）的强化程序下自我给药可卡因（0.3毫克/千克/输注），然后在渐进比率（PR）强化程序下连续测试六天。在FR强化程序的自我给药训练期间，未观察到组间差异。然而，在PR程序测试时，VTA注射AMPH预处理的大鼠比注射生理盐水预处理的大鼠工作更多，因此获得了更多的可卡因输注。单独一组预先接受VTA注射AMPH但同时注射D（1）样多巴胺（DA）受体拮抗剂SCH23390（0.25微克/0.5微升/侧）的大鼠并未表现出可卡因自我给药增强。这些大鼠以及其他仅预先接受VTA注射SCH23390的大鼠表现出的可卡因自我给药水平与注射生理盐水预处理的大鼠相似。因此，与AMPH诱导的运动和伏隔核DA溢出的敏化方式相似，之前VTA注射AMPH会导致可卡因静脉自我给药增强，并且在此部位预先暴露期间D（1）DA受体的激活对于产生这种效应是必要的。
