Muscimol state-dependent memory: involvement of dorsal hippocampal mu-opioid receptors

In the present study, the effects of subcutaneous (s.c.) injections of morphine, a mu-opioid receptor agonist and intra-dorsal hippocampal (intra-CA1) injections of naloxone, a mu-opioid receptor antagonist on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-CA1 administration of a GABAA receptor agonist, muscimol (0.025, 0.05, 0.1 and 0.2 microg/mouse) dose dependently induced impairment of memory retention. Pre-test injection of muscimol (0.05, 0.1 and 0.2 microg/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under pre-training muscimol (0.1 microg/mouse, intra-CA1) influence. Pre-test injection of morphine (0.5 and 1 mg/kg, s.c.) 30 min before the administration of muscimol (0.1 microg/mouse, intra-CA1) dose dependently inhibited muscimol state-dependent memory. Pre-test intra-CA1 injection of naloxone (0.1 and 0.2 microg/mouse, intra-CA1) improved pre-training muscimol (0.1 microg/mouse)-induced retrieval impairment. Moreover, pre-test administration of naloxone (0.1 and 0.2 microg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 microg/mouse) significantly restored the retrieval and induced muscimol state-dependent memory. These findings implicate the involvement of a dorsal hippocampal mu-opioid receptor mechanism in muscimol state-dependent memory.