Involvement of dorsal hippocampal muscarinic cholinergic receptors on muscimol state-dependent memory of passive avoidance in mice

Abstract

Aims In the present study, the effects of bilateral intra-dorsal hippocampal (intra-CA1) injections of cholinergic agents on muscimol state-dependent memory were examined in mice. Main methods A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Key findings Pre-training intra-CA1 administration of a GABA-A receptor agonist, muscimol (0.05 and 0.1 μg/mouse) dose dependently induced impairment of memory retention. Pre-test injection of muscimol (0.05 and 0.1 μg/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under pre-training muscimol (0.1 μg/mouse, intra-CA1) influence. Pre-test intra-CA1 injection of an acetylcholinesterase inhibitor, physostigmine (0.5 and 1 μg/mouse, intra-CA1) reversed the memory impairment induced by pre-training administration of muscimol (0.1 μg/mouse, intra-CA1). Moreover, pre-test administration of physostigmine (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 μg/mouse, intra-CA1) significantly restored the retrieval and induced muscimol state-dependent memory. Pre-test intra-CA1 administration of physostigmine (0.25, 0.5 and 1 μg/mouse) by itself cannot affect memory retention. Pre-test intra-CA1 injection of the muscarinic receptor antagonist, atropine (1 and 2 μg/mouse) 5 min before the administration of muscimol (0.1 μg/mouse, intra-CA1) dose dependently inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of atropine (0.5, 1 and 2 μg/mouse) by itself cannot affect memory retention. Significance The results suggest that muscarinic cholinergic mechanism of the CA1 may influence muscimol state-dependent memory.