Del Olmo N, Higuera-Matas A, Miguéns M, García-Lecumberri C, Ambrosio E
Departamento Psicobiología, Facultad de Psicología, UNED, C/ Juan del Rosal no 10, 28040, Madrid, Spain.
Psychopharmacology (Berl). 2007 Nov;195(1):19-25. doi: 10.1007/s00213-007-0873-1. Epub 2007 Jul 20.
Long-term potentiation (LTP) is considered to be a cellular substrate of learning and memory. Indeed, the involvement of LTP-like mechanisms in spatial learning has consistently been demonstrated in the Morris water maze test. We have previously shown that hippocampal LTP in Lewis rats was modulated by cocaine self-administration, although the performance of cocaine-self-administered rats in the Morris water maze was not altered.
Given that the ease of the task previously used could have masked any possible effects of the cocaine-induced LTP enhancement on spatial learning, a new and more difficult water maze task was devised to address this issue.
Animals self-administered cocaine (1 mg/kg) or saline under a fixed ratio 1 schedule of reinforcement for 22 days. Spatial learning was assessed in a difficult water maze task (four sessions, two trials per session with a 90-min intertrial interval), and spatial memory was also evaluated 48 h after training (a 90-s test). Additionally, reversal learning and perseverance were also studied.
There was a reduced latency in finding the hidden platform during training, as well as improved memory of the platform location in cocaine-self-administered rats with respect to animals that self-administered saline. No differences were observed in reversal learning or perseverance between groups.
Our data suggest that cocaine self-administration facilitates learning and memory in the water maze test only when animals are submitted to highly demanding tasks, involving working memory or consolidation-like processes during the intertrial interval.
长时程增强(LTP)被认为是学习和记忆的细胞基础。事实上,在莫里斯水迷宫试验中,类似LTP的机制参与空间学习这一点已得到持续证实。我们之前已表明,可卡因自我给药可调节刘易斯大鼠的海马LTP,尽管可卡因自我给药大鼠在莫里斯水迷宫中的表现未发生改变。
鉴于之前使用的任务较为简单,可能掩盖了可卡因诱导的LTP增强对空间学习的任何潜在影响,因此设计了一项新的、更具难度的水迷宫任务来解决这一问题。
动物按照固定比率1强化程序自我给药可卡因(1毫克/千克)或生理盐水,持续22天。在一项难度较大的水迷宫任务中评估空间学习能力(共四节,每节两次试验,试验间隔90分钟),并在训练后48小时评估空间记忆(90秒测试)。此外,还研究了逆向学习和坚持性。
与自我给药生理盐水的动物相比,可卡因自我给药大鼠在训练期间找到隐藏平台的潜伏期缩短,并对平台位置的记忆得到改善。两组在逆向学习或坚持性方面未观察到差异。
我们的数据表明,仅当动物接受要求苛刻的任务时,可卡因自我给药才会促进水迷宫试验中的学习和记忆,这些任务在试验间隔期间涉及工作记忆或类似巩固的过程。