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 alpha1-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 alpha1-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 alpha1-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.
Malinowska
B
B
Department of Experimental Physiology, Medical University in Białystok, Poland. bmalin@ckrs.ac.bialystok.pl
Napiórkowska-Pawlak
D
D
Pawlak
R
R
Buczko
W
W
Göthert
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D012640:Seizures / Q000517:prevention & control; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D000431:Ethanol; C010739:ifenprodil; D011224:Prazosin