Effect of ethanol on morphine state-dependent learning in the mouse: Involvement of gabaergic, opioidergic and cholinergic systems

Aims: We have studied the effect of acute administration of ethanol when it replaced morphine in step-down passive avoidance task on the test day and the effects of antagonists of GABAergic, opioidergic and cholinergic systems on ethanol actions. Methods: Morphine (5 mg/kg, s.c.) was administered as pre-training and 24 h later as pre-test drug, and the latencies were measured in mice. Ethanol (0.125, 0.25, 1 and 2 g/kg, i.p.) was administered instead of pre-test morphine. Antagonists of GABAergic (bicuculline 0.5, 1 and 2 mg/kg, i.p.), opioidergic (naloxone 0.06, 0.25 and 1 mg/kg, i.p.) and cholinergic (atropine 0.625 and 1.25 mg/kg, i.p. and mecamylamine 0.5, 1 and 2 mg/kg, i.p.) systems were co-administered with ethanol (0.25 g/kg, i.p.) on the test day. Locomotor activity was measured as well. Results: Pre-training morphine impaired the memory on the test day which was restored when the same dose of morphine was used as pre-test drug. All four doses of ethanol replaced pre-test morphine and enhanced the memory. This effect was prevented by all of the above antagonists. No significant changes were seen in the locomotor activity of the animals treated with ethanol or antagonists compared to the proper controls. Conclusions: GABAergic, endogenous opioidergic and cholinergic systems are involved in the memory recall improvement by ethanol when it replaced morphine on the test day. A review of the literature suggests other possibilities such as the release of intermediate neurotransmitters.