Involvement of Median Septum Region in Ghrelin Effects on Morphine-Induced Memory Impairment in Passive Avoidance Learning

Background and purpose: Many studies have reported the effect of morphine on memory impairment. Evidence suggests that ghrelin enhances memory consolidation. The median septum also has a major role in memory and learning mechanisms. The present study aimed at investigating the role of median septum on the effects of ghrelin in morphine-induced amnesia. Materials and methods: In this experimental research, male Wistar rats were randomly divided into 12 groups: ghrelin groups (0, 0.3, 1.5, 3 nmol/µl) plus saline (1 ml/kg) or morphine (7.5 mg/kg) and groups treated with lidocaine (1 μl/rat) or saline (1 μl/rat) plus ghrelin (3 nmol/μl) or saline (1 μl/rat) plus morphine (7.5 mg/kg). Cannulation was done in the lateral ventricle and median septum. Ghrelin and lidocaine were injected into the lateral ventricle and septum, respectively and morphine was injected subcutaneously. Memory was assessed by avoidant learning. Results: Post-training intra-ventricle administration of ghrelin 5 min prior to morphine (7.5 mg/kg) prevented morphine amnesia (P= 0.000). Injection of lidocaine into the median septum 5 min before the injection of ghrelin prevented its effect on inhibition of morphine amnesia (P= 0.000). Conclusion: Injection of ghrelin into the lateral ventricle was found to be capable of preventing morphine-induced memory impairment. Inactivation of the median septum by injection of lidocaine reduced the effect of ghrelin on morphine-induced memory deficits. Therefore, the median septal region appears to mediate the effects of ghrelin on morphine-induced amnesia.