Solecki Wojciech, Krowka Tomasz, Kubik Jakub, Kaczmarek Leszek, Przewlocki Ryszard
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Science, 12 Smetna Street, 31-343 Krakow, Poland.
Behav Brain Res. 2008 Jul 19;190(2):212-7. doi: 10.1016/j.bbr.2008.02.040. Epub 2008 Mar 6.
The immediate early genes (IEGs) have been suggested to be implicated in mechanisms of addiction, as well as in learning and memory processes. fosB, which belongs to IEG, has been reported to have pleiotropic impact on response to psychoactive drugs, as well as motivational and stress-related behaviours. In the present study, we used mice with constitutive knock-out of fosB in order to study fosB role in mouse phenotype. We studied rewarding properties of morphine (10mg/kg i.p.) in conditioned place preference (CPP) paradigm. Additionally, we studied fosB role in spatial memory and spatial working memory using elevated plus maze model of spatial learning (EPMSL) and delayed non-match to place task (DNMTP). In further studies, locomotor, depressive-like and anxiety-like behaviours were measured. Rewarding effects of morphine in fosB -/- mice were abolished whereas spatial learning was impaired. On the other hand, we found no significant differences in locomotor activity, depression-like and anxiety-like behaviours. In summary, our results indicate that mice lacking fosB are less sensitive to rewarding properties of morphine and display spatial memory impairment and suggest involvement of fosB and its proteins in motivational aspects of reinforcers as well as in learning and memory processes.
即刻早期基因（IEGs）被认为与成瘾机制以及学习和记忆过程有关。fosB属于即刻早期基因，据报道它对精神活性药物的反应以及动机和应激相关行为具有多效性影响。在本研究中，我们使用了fosB基因组成型敲除的小鼠来研究fosB在小鼠表型中的作用。我们在条件性位置偏爱（CPP）范式中研究了吗啡（10mg/kg腹腔注射）的奖赏特性。此外，我们使用空间学习高架十字迷宫模型（EPMSL）和延迟位置不匹配任务（DNMTP）研究了fosB在空间记忆和空间工作记忆中的作用。在进一步的研究中，测量了运动、抑郁样和焦虑样行为。fosB基因敲除小鼠中吗啡的奖赏效应被消除，而空间学习受损。另一方面，我们发现运动活性、抑郁样和焦虑样行为没有显著差异。总之，我们的结果表明，缺乏fosB的小鼠对吗啡的奖赏特性不太敏感，并表现出空间记忆受损，提示fosB及其蛋白参与了强化物的动机方面以及学习和记忆过程。
