Introduction: Ghrelin is a peptide mainly produced by the stomach and released into the circulation, affecting energy balanced and growth hormone release. It is well known that learning and memory in labratory animals can be affected by ghrelin treatment. The extensive evidence that the Medial Septum is involved in the process of learning and memory. In this study we examined the involvement of the Medial Septum on ghrelin effects on morphine induced memory impairment in male rats. Materials and Methods: Adult male Wistar rats (Pasteur institute, Tehran, Iran) weighing 220–250 g at the time of surgery were used. In all groups, cannulation was performed in the Medial Septum and the memory of the rats was assessed by inhibitory avoidance test. Experimental groups consist of saline group (1ml/kg, s.c.), morphine groups (0.5, 2.5, 5, 7.5 mg/kg, s.c.) and treated groups with ghreline (0.1, 0.3, 1 nmol/µl- intra-MS) plus saline (1 ml/kg, s.c.) or morphine (7.5 mg/kg, s.c.). All animals were tested after 24 h and step-through latency of each animal was recorded. Data were statistically evaluated by analysis of variance and followed by Tukey test. In all comparisons, P<0.05 was considered as the statistical significance level. Results: Post-training subcutaneous administration of different doses of morphine dose dependently decreased the learning and induced amnesia (p<0.001). Intra- Medial Septum injections of ghrelin 5 minutes before the injection of effective dose of morphine (7.5 mg/kg) dose dependently restored the memory retieval (p<0.001). Discussion: The results suggested that learning and memory can effecte by ghrelin. Intra- Medial Septum administration of ghrelin after training improved morphine-induced memory impairment.
