Department of Psychology, University of Houston, Houston, Texas.
Am J Addict. 2021 Jul;30(4):358-365. doi: 10.1111/ajad.13152. Epub 2021 Apr 2.
Chronic cocaine exposure has differential neural effects in Fischer 344 (F344) vs Lewis inbred rats that may explain strain-dependent differences during acquisition vs maintenance of cocaine self-administration. We assessed whether prior cocaine exposure alters operant responding for food across various phases (acquisition, maintenance, extinction, spontaneous recovery, reinitiation) in these strains.
Lewis and F344 rats (N = 12) were administered three cocaine (15 mg/kg) or saline injections at hourly intervals for 3 consecutive days. Beginning the next day for 24 days, rats had access to operant chambers in which one lever depression resulted in the delivery of a food pellet. Then, four extinction sessions were conducted in which food was no longer available, but other stimulus conditions remained the same. After a 2-day break, spontaneous recovery was assessed over four sessions. Food delivery was then restored for 3 days to test reinitiation followed by a progressive ratio session.
Lewis rats acquired the operant faster than F344 rats. F344 rats showed lower maintenance rates than Lewis rats but higher spontaneous recovery responding. Cocaine exposure caused persistence of responding during extinction in F344 but not Lewis rats. All groups reinitiated responding when food was available again and did not differ in final ratios completed under the progressive ratio schedule.
That prior cocaine exposure led to persistence of responding in F344 rats during extinction may reflect heightened contextual conditioning that interferes with the ability to extinguish responding.
Results have implications for the genetic contribution to relapse-like behaviors. (Am J Addict 2021;00:00-00).
慢性可卡因暴露对 Fischer 344（F344）和 Lewis 近交系大鼠的神经有不同影响，这可能解释了在可卡因自我给药的获得和维持过程中，不同品系之间的差异。我们评估了在这些品系中，先前的可卡因暴露是否会改变操作反应在各个阶段（获得、维持、消退、自发恢复、重新启动）的食物。
Lewis 和 F344 大鼠（N=12）在连续 3 天内每小时接受 3 次可卡因（15mg/kg）或盐水注射。从第二天开始，24 天内，大鼠可以进入操作室，其中一次压杆会导致一个食物丸的输送。然后，进行了 4 次消退会话，在这些会话中不再提供食物，但其他刺激条件保持不变。休息两天后，评估了 4 次自发恢复。然后恢复食物供应 3 天，以测试重新启动，然后进行递增比率测试。
Lewis 大鼠比 F344 大鼠更快地获得了操作反应。F344 大鼠的维持率低于 Lewis 大鼠，但自发恢复反应较高。可卡因暴露导致 F344 大鼠在消退期间反应持续，而 Lewis 大鼠则没有。当食物再次可用时，所有组都重新开始反应，并且在递增比率计划下完成的最终比率没有差异。
先前的可卡因暴露导致 F344 大鼠在消退期间的反应持续，这可能反映了增强的上下文条件作用，干扰了消退反应的能力。
结果对遗传因素对复发性行为的影响有启示。（美国成瘾杂志 2021；00：00-00）。
