Ifenprodil influences changes in mouse behaviour related to acute and chronic ethanol administration

The aim of the present study was to examine the influence of ifenprodil (a non-competitive NMDA receptor antagonist which also blocks 5-HT3 receptors and alpha c(1)-adrenoceptors) on the effects of ethanol in the mouse in vivo and to elucidate the role of various receptors in these actions. The ethanol (4 g/kg i.p.)-induced sleeping time was shortened by ifenprodil 1 mg/kg but was not affected by ifenprodil 0.3 mg/kg, the 5-HT3 receptor antagonist ondansetron 0.03 mg/kg and the non-competitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a, d)cycloheptan-5, 10-imine maleate) 0.01 mg/kg. Ifenprodil 10 mg/kg mimicked the alpha(1)-, adrenoceptor antagonist prazosin 1 mg/kg in that it prolonged the hypnotic response to ethanol (no additive effect when both drugs were given in combination); this is compatible with an involvement of alpha(1)-adrenoceptors in this effect of ifenprodil. Chronic exposure to ethanol (7%) induced physical dependence. The severity of ethanol withdrawal was suppressed by ifenprodil 1 and 10 mg/kg. In conclusion, ifenprodil influences ethanol-related changes in mouse behaviour and may prove to be useful in the treatment of alcoholism. (C) 1999 Elsevier Science B.V. All rights reserved.