Introduction: The medial septum (MS) region plays a key role in learning and memory mechanism. Memory deficit is one of the side effects of morphine. Ghrelin hormone increases memory retention. The aim of the present study is the investigation of the role of medial septum in ghrelin-induced improvement effect on morphine-induced amnesia. Materials and methods: In this experimental study, 119 male Wistar rats (220-250 gr) were randomly divided into 17 groups including: saline (1 ml/kg), morphine treated groups (0.5, 2/5, 5,7.5 mg/kg), ghrelin treated groups (0, 0/3, 1/5, 3 nmol/µl) plus saline (1 ml/kg) or morphine (7.5 mg/kg) and groups treated whit lidocaine (1 μl/rat) or saline (1 μl/rat) + ghrelin (3 nmol/μl) or saline (1 μl/rat) + morphine (7.5 mg/kg). The rats were implanted by two separate cannulas into the MS and lateral ventricle regions. Morphine was injected subcutaneously, ghrelin and lidocaine were locally injected into the ventricle and MS regions, respectively. Data were analyzed using ANOVA (one way and two ways) analysis followed by Tukey’s multiple comparison test (p< 0.05). Results: Post-training administration of morphine dose-depndently reduced the step-through latency and induced amnesia (p< 0.001). Post-training intra-ventricle administration of ghrelin prior to morphine (7.5 mg/kg) decreased prevented the improving effect of ghrelin on amnesia induced by morphine (p< 0.001). Injection of lidocaine intra medial septum prevented the effect of ghrelin on morphine amnesia (p< 0.001). Conclusion: These finding indicate that the MS is involved in mediating the modulatory effect of ghrelin on morphine-induced amnesia.
