Attenuation of the acute amnestic effect of ethanol by ifenprodil: comparison with ondansetron and dizocilpine.
The aim of the present study was to examine the influence of ifenprodil, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which also blocks 5-HT3 receptors, on the amnestic effect of ethanol in a passive avoidance task in mice. The anti-amnestic action of ifenprodil was compared with the effects of the 5-HT3 receptor antagonist ondansetron and the non-competitive NMDA-receptor antagonist dizocilpine (MK-801). Ethanol, 2 g/kg and dizocilpine 0.1 mg/kg significantly impaired the passive avoidance response. In contrast, ifenprodil (0.1-10 mg/kg), ondansetron (0.03-0.3 mg/kg) and dizocilpine (0.01 and 0.03 mg/kg) did not alter passive avoidance by themselves. Dizocilpine did not diminish the amnestic action of ethanol when administered at doses of 0.03-0.1 mg/kg. However, the amnestic effect of ethanol was partially restored towards normal by ifenprodil 0.3 mg/kg and by ondansetron 0.03 mg/kg (alone or together with dizocilpine 0.01 mg/kg) but it was not affected by other doses of ifenprodil (0.1, 1 and 10 mg/kg) and ondansetron (0.1 and 0.3 mg/kg). In conclusion, ifenprodil at an appropriate dose reduced ethanol-induced amnesia in a step-through passive avoidance task. The results are compatible with the assumption that the anti-amnestic action of ifenprodil may be (at least partially) due to an antagonism at 5-HT3 receptors.
Napiórkowska-Pawlak
D
D
Department of Experimental Physiology, Medical Academy in Bialystok, Mickiewicza, Poland.
Malinowska
B
B
Pawlak
R
R
Buczko
W
W
Göthert
M
M
D000208:Acute Disease; D000647:Amnesia / Q000139:chemically induced / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D017294:Ondansetron / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011930:Reaction Time; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists; D000431:Ethanol; D017294:Ondansetron; D016291:Dizocilpine Maleate; C010739:ifenprodil