Involvement of μ 1-opioid receptors and cholinergic neurotransmission in the endomorphins-induced impairment of passive avoidance learning in mice

Abstract

The effects of naloxonazine, a μ 1-opioid receptor antagonist, and physostigmine, a cholinesterase inhibitor, on the endomorphins-induced impairment of passive avoidance learning were investigated in mice. Endomorphin-1 (10 μg) and endomorphin-2 (10 μg) significantly impaired passive avoidance learning, while naloxonazine (35 mg/kg, s.c.), a μ 1-opioid receptor antagonist, which alone failed to influence passive avoidance learning significantly inhibited the endomorphin-1 (10 μg)- but not endomorphin-2 (10 μg)-induced disturbance of such learning. A rather nonselective higher dose (50 mg/kg, s.c.) of naloxonazine almost completely antagonized the endomorphin-1 (10 μg)- and endomorphin-2 (10 μg)-induced impairment of passive avoidance learning. In contrast, physostigmine (0.025 and 0.05 mg/kg, i.p.) significantly reversed the endomorphin-1 (10 μg)- and endomorphin-2 (10 μg)-induced disturbance of passive avoidance learning, whereas physostigmine (0.025 and 0.05 mg/kg, i.p.) alone did not influence such learning. These results suggest that endomorphin-1 but not endomorphin-2 impairs learning and memory resulting from cholinergic dysfunction, and from activation of μ 1-opioid receptors.