Ghrelin modulates morphine-nicotine interaction in avoidance memory: Involvement of CA1 nicotinic receptors.

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.