Fole Alberto, Miguéns Miguel, Morales Lidia, González-Martín Carmen, Ambrosio Emilio, Del Olmo Nuria
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Spain.
Departamento de Psicología Básica I, Facultad de Psicología, Universidad Nacional de Educación a Distancia (UNED), Spain.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jun 2;76:49-57. doi: 10.1016/j.pnpbp.2017.02.024. Epub 2017 Mar 2.
Lewis (LEW) and Fischer 344 (F344) rats are considered a model of genetic vulnerability to drug addiction. We previously showed important differences in spatial learning and memory between them, but in contrast with previous experiments demonstrating cocaine-induced enhanced learning in Morris water maze (MWM) highly demanding tasks, the eight-arm radial maze (RAM) performance was not modified either in LEW or F344 rats after chronic cocaine treatment. In the present work, chronically cocaine-treated LEW and F344 adult rats have been evaluated in learning and memory performance using the Y-maze, two RAM protocols that differ in difficulty, and a reversal protocol that tests cognitive flexibility. After one of the RAM protocols, we quantified dendritic spine density in hippocampal CA1 neurons and compared it to animals treated with cocaine but not submitted to RAM. LEW cocaine treated rats showed a better performance in the Y maze than their saline counterparts, an effect that was not evident in the F344 strain. F344 rats significantly took more time to learn the RAM task and made a greater number of errors than LEW animals in both protocols tested, whereas cocaine treatment induced deleterious effects in learning and memory in the highly difficult protocol. Moreover, hippocampal spine density was cocaine-modulated in LEW animals whereas no effects were found in F344 rats. We propose that differences in addictive-like behavior between LEW and F344 rats could be related to differences in hippocampal learning and memory processes that could be on the basis of individual vulnerability to cocaine addiction.
刘易斯（LEW）大鼠和费希尔344（F344）大鼠被认为是对药物成瘾具有遗传易感性的模型。我们之前发现它们在空间学习和记忆方面存在重要差异，但与之前在莫里斯水迷宫（MWM）高要求任务中证明可卡因诱导学习增强的实验不同，慢性可卡因处理后，LEW或F344大鼠在八臂放射状迷宫（RAM）中的表现并未改变。在本研究中，使用Y迷宫、两种难度不同的RAM方案以及一种测试认知灵活性的反转方案，对慢性可卡因处理的成年LEW和F344大鼠的学习和记忆表现进行了评估。在其中一种RAM方案后，我们对海马CA1神经元中的树突棘密度进行了量化，并将其与接受可卡因处理但未进行RAM实验的动物进行了比较。接受可卡因处理的LEW大鼠在Y迷宫中的表现优于其生理盐水对照组，而这种效应在F344品系中并不明显。在两种测试方案中，F344大鼠学习RAM任务的时间明显比LEW动物长，且犯错次数更多，而在高难度方案中，可卡因处理对学习和记忆产生了有害影响。此外，LEW动物的海马棘密度受到可卡因的调节，而在F344大鼠中未发现影响。我们认为，LEW和F344大鼠在成瘾样行为上的差异可能与海马学习和记忆过程的差异有关，而这可能是个体对可卡因成瘾易感性的基础。
