Role of hippocampal M1 and M4 muscarinic receptor subtypes in memory consolidation in the rat

Muscarinic receptors in the hippocampus are relevant to learning and memory, but the role of each subtype is poorly understood. Muscarinic toxins (MTs) from Dendroaspis snakes venom are selective for muscarinic receptor subtypes. MT2, a selective agonist for M1 receptors, given into the hippocampus immediately after training, improved memory consolidation of an inhibitory avoidance task in rats, whereas the antagonist pirenzepine was amnestic, supporting a facilitatory role of M1 receptors. Instead, MT3, a selective antagonist at M4 receptors, caused amnesia. Neither M1 nor M4 receptor appeared involved in habituation to a new environment. Thus, our results suggest that memory consolidation of an inhibitory avoidance task in the rat involves the participation of both M1 and M4 hippocampal receptors, with a positive modulatory role.