RESUMO
Introduction: Evidence indicates that medial septum nicotinic receptors regulate cognitive processes. Ghrelin is a gut hormone that regulates energy homeostasis. Ghrelin is also produced in the brain and is involved in cognitive function. This study aims to evaluate the effects of medial septal administration of ghrelin on the amnestic effect of morphine in rats. In addition, the possible relationship between the medial septal ghrelin and acetylcholine nicotinic receptors on the amnestic effect of morphine is evaluated. Methods: The rats were implanted at the medial septum area and were microinjected with ghrelin and nicotinic receptor agents. The step-through type inhibitory avoidance apparatus was used for memory retrieval assessment. Results: The results showed that the administration of morphine after the training phase impaired memory consolidation. Post-training intra-septal injection of the same doses of either ghrelin or nicotine did not change memory performance; however, their co-application with morphine (significant dose: 7.5 mg/kg subcutaneous injection) increased the step-through latency and improved memory consolidation. Moreover, post-training co-application of low doses of the two agonists could not affect morphine-induced memory impairment. Conclusion: These results indicated no interaction between medial septal ghrelin and nicotinic receptors on the amnestic effect of morphine in rats. Highlights: Post-training morphine administration impaired memory performance.Intra-septal injection of ghrelin or nicotine alone did not affect memory performance.Co-application of either ghrelin or nicotine with morphine improved memory.Co-application of the two agents could not affect morphine-induced memory impairment. Plain Language Summary: Morphine abuse has been associated with memory disturbance. Ghrelin is a gastrointestinal hormone known as hunger hormone. It also affects cognitive performance via binding ghrelin receptors in central nervous system. On the other hand, the medial septum nicotinic receptors improve memory-associated behavior. Hence, we hypothesized that septal ghrelin receptors could affect the effect of nicotine on morphine-induced memory deficit. We examined this hypothesis in avoidance memory task. We found that subcutaneous administration of morphine inhibited avoidance memory. The effect of morphine was blocked by intra-medial septum injection of nicotine or ghrelin. However, co-infusion of ghrelin with nicotine into the medial septum area had no effect on morphine amnesia. Overall, the study results suggest no interaction between ghrelin and cholinergic nicotinic receptors in morphine amnesia.
