Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4A, PL 20-093 Lublin, Poland.
Pharmacol Rep. 2011;63(6):1372-82. doi: 10.1016/s1734-1140(11)70701-0.
The purpose of our experiments was to examine the influence of cholinergic receptor ligands on memory-related behavior in mice using the elevated plus maze (EPM) test. The EPM test allows the exploration of different memory processes (acquisition and consolidation), depending on the time of drug treatment. The time necessary for mice to move from the opened arm to the enclosed arm (i.e., transfer latency, TL) was used as an index of memory. Our findings reveal that for both the processes of acquisition and consolidation, treatment with nicotine (0.035 or 0.175 mg/kg, free base, sc) shortened TL on the second day of the experiments (TL2), thus improving memory processes. Treatment with scopolamine (0.3 or 1.0 mg/kg, ip) significantly increased TL2 values, thus impairing cognitive processes. Moreover, we found that treatment with nicotine, at the non-effective doses used during testing, prevented scopolamine-induced memory impairment by inducing a decrease in TL2 values. Next, we evaluated the influence of bupropion (10 or 20 mg/kg, ip), a drug currently used for smoking cessation in humans, on memory-related behavior induced by treatment with nicotine and scopolamine. An acute injection of bupropion (10 or 20 mg/kg) prior to injection with either nicotine (0.035 mg/kg) or scopolamine (1.0 mg/kg) significantly prevented nicotine-induced memory improvement or scopolamine-induced memory impairment. Bupropion treatment can diminish the rewarding (dependence-producing) effects of nicotine and also the cognitive effects that are related to addiction. Our studies further indicate the great involvement of the cholinergic system in memory processes and the potential for the development of more effective pharmacotherapies for memory impairment-like human disorders in which the cholinergic pathways have been implicated.
我们的实验目的是使用高架十字迷宫（EPM）测试研究胆碱能受体配体对小鼠记忆相关行为的影响。EPM 测试允许根据药物治疗时间探索不同的记忆过程（获得和巩固）。从开放臂移动到封闭臂所需的时间（即转移潜伏期，TL）被用作记忆的指标。我们的研究结果表明，对于获得和巩固这两个过程，尼古丁（0.035 或 0.175mg/kg，游离碱，sc）治疗在实验的第二天缩短了 TL2，从而改善了记忆过程。东莨菪碱（0.3 或 1.0mg/kg，ip）治疗显著增加了 TL2 值，从而损害了认知过程。此外，我们发现，在测试中使用的非有效剂量下，尼古丁治疗可通过降低 TL2 值来预防东莨菪碱引起的记忆障碍，从而防止东莨菪碱引起的记忆障碍。接下来，我们评估了目前用于人类戒烟的药物丁丙诺啡（10 或 20mg/kg，ip）对尼古丁和东莨菪碱处理引起的记忆相关行为的影响。在注射尼古丁（0.035mg/kg）或东莨菪碱（1.0mg/kg）之前，丁丙诺啡（10 或 20mg/kg）的急性注射显著防止了尼古丁诱导的记忆改善或东莨菪碱诱导的记忆损伤。丁丙诺啡治疗可以减轻尼古丁的奖赏（产生依赖性）作用，以及与成瘾相关的认知作用。我们的研究进一步表明，胆碱能系统在记忆过程中具有重要作用，并且有可能开发出更有效的治疗药物来治疗类似人类的记忆障碍，其中胆碱能途径已经被牵连。
