Department of Biology, Payame Noor University (PNU), Tehran, Iran.
Department of Biology, Faculty of Science, Arak University, Arak 38156-8-8349, Iran.
Brain Res. 2019 Oct 1;1720:146315. doi: 10.1016/j.brainres.2019.146315. Epub 2019 Jun 28.
Ghrelin is a stomach-derived hormone which regulates appetite and energy balance in the body. Recent studies show that ghrelin has been linked to the learning and memory process. Ghrelin also modulates reward properties of addictive drugs. However, the involvement of ghrelin in cognitive effects of addictive drugs has not been examined yet. The goal of present study is to examine the effect of intra-CA1 administration of ghrelin on morphine response for avoidance task alone or in combination with nicotine. Here, we also investigated the role of hippocampal nicotinic cholinergic receptors in possible interaction of the drugs in adult male Wistar rats. Results showed that subcutaneous administration of morphine immediately after training impaired memory in the test day and induced amnesia, while intra-CA1 pre-injection of ghrelin prevented amnesic effect of morphine and improved memory. Also, systemic administration of nicotine five min prior to morphine administration dose-dependently inhibited morphine-induced amnesia. The results showed that intra-CA1 injection of an ineffective dose of ghrelin (0.03 nmol/µl) potentiated the nicotine (0.2 mg/kg, s.c.) response on amnesia induced by morphine. This stimulatory effect was inhibited by mechamylamine, a non-competitive nicotinic receptor antagonist. Moreover, post-training administration of drugs (ghrelin, nicotine and mecamylamine) alone had no effect on memory consolidation. In conclusion, present study suggests the significant role of ghrelin in morphine-related memory and its interactive effect with nicotine in avoidance task via CA1 nicotinic receptors.
胃饥饿素是一种由胃分泌的激素，可调节体内的食欲和能量平衡。最近的研究表明，胃饥饿素与学习和记忆过程有关。胃饥饿素还调节成瘾药物的奖赏特性。然而，胃饥饿素在成瘾药物的认知效应中的作用尚未被研究。本研究的目的是研究 CA1 内给予胃饥饿素对单独或与尼古丁联合使用吗啡回避任务的反应的影响。在这里，我们还研究了海马烟碱型乙酰胆碱受体在药物相互作用中的作用，在成年雄性 Wistar 大鼠中。结果表明，训练后立即皮下给予吗啡会损害测试日的记忆，引起健忘症，而 CA1 内预先给予胃饥饿素可防止吗啡引起的健忘症并改善记忆。此外，在给予吗啡之前 5 分钟给予系统给予尼古丁可剂量依赖性地抑制吗啡引起的健忘症。结果表明，CA1 内注射无效剂量的胃饥饿素（0.03 nmol/µl）可增强尼古丁（0.2 mg/kg，sc）对吗啡引起的健忘症的反应。这种刺激作用被非竞争性烟碱受体拮抗剂美加明抑制。此外，单独给予药物（胃饥饿素、尼古丁和美加明）后训练对记忆巩固没有影响。总之，本研究表明胃饥饿素在吗啡相关记忆中具有重要作用，并且通过 CA1 烟碱型乙酰胆碱受体与尼古丁相互作用。
