Kisspeptin-13 ameliorates memory impairment induced by streptozotocin in male rats via cholinergic system

Introduction: Kisspeptin-13 (KP-13) is a novel endogenous factor, increases synaptic transmission and is involved in several behavioral functions such as anxiety, locomotion, epilepsy and avoidance learning. However, the role of this peptide on cognition has not been well clarified yet. Here we studied the effect of kisspeptin-13 pretreatment on spatial learning and also interaction with cholinergic and adrenergic systems. Methods: Eighty adult male Wistar rats were divided into 10 groups: saline + saline; saline + STZ; KP-13 + STZ; propranolol + STZ; prazosin + STZ; atropine + STZ; saline + KP-13 + STZ; propranolol + KP-13 + STZ; prazosin + KP-13 + STZ; atropine + KP-13+ STZ. Streptozotocin (STZ) (3mg/Kg) was administrated intracerebroventricularly (i.c.v), kisspeptin-13 was infused (1µg/2µl, i.c.v) 30 minutes before STZ and antagonists were infused (i.p) 30 minutes before kisspeptin-13. Memory performance was measured 14 days after STZ injection using Morris Water Maze (MWM) consisting of 4 blocks and one probe tests. Results: Pretreatment with kisspeptin-13 ameliorated acquisition (p = 0.001) and retrieval of memory impaired by STZ (P = 0.011). Moreover, we found that injection of atropine, but not propranolol or prazocin was able to reverse the memory enhancement caused by kisspeptin-13 (P = 0.037). Conclusion: Our findings indicate that facilitatory action of kisspeptin-13 on the spatial learning and memory in STZ-induced Alzheimer’s is mediated, at least in part, through cholinergic systems.