Alcohol and Alcoholism Advance Access originally published online on August 2, 2004
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Alcohol & Alcoholism Vol. 39, No. 5, pp. 427-432, 2004
Alcohol & Alcoholism Vol. 39, No. 5 © Medical Council on Alcohol 2004; all rights reserved
EFFECT OF ETHANOL ON MORPHINE STATE-DEPENDENT LEARNING IN THE MOUSE: INVOLVEMENT OF GABAERGIC, OPIOIDERGIC AND CHOLINERGIC SYSTEMS
1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, 2 School of Medicine, Tehran University of Medical Sciences, Tehran and 3 Department of Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
* Author to whom correspondence should be addressed at: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145–784, Tehran, Iran. Tel.: +98 21 611 2801; Fax: +98 21 640 2569; E-mail: zarinmr{at}ams.ac.ir
(Received 19 February 2004; first review notified 2 April 2004; in revised form 6 May 2004; accepted 21 June 2004)
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.