Ethanol behaves as an NMDA antagonist with respect to locomotor stimulation in monoamine-depleted mice.
Previous studies have shown that administration of NMDA antagonists in combination with the alpha 2-adrenoceptor agonist clonidine results in a marked locomotor stimulation in monoamine-depleted mice, albeit the pattern of movement produced is highly stereotyped and primitive. Ethanol has recently been suggested to display NMDA antagonistic properties; hence, in the present study the ability of ethanol to produce locomotor activation in monoamine-depleted mice with a movement pattern similar to that produced by NMDA antagonists was investigated. It was found that neither ethanol nor clonidine given alone reversed the akinesia induced by pretreatment with reserpine (10 mg/kg; 18 h) and alpha-methyl-para-tyrosine (500 mg/kg; 2 h). However, when the drugs were combined a marked stimulatory effect was observed and, indeed, the animals displayed the same primitive locomotor pattern previously observed following treatment with NMDA antagonists in conjunction with clonidine. The locomotor response was effectively blocked by pretreatment with the selective alpha 2-adrenoceptor antagonists yohimbine (10 mg/kg) or idazoxan (10 mg/kg) but not with the selective alpha 1-adrenoceptor antagonist prazosin (1 mg/kg). The present results suggest that ethanol in conjunction with alpha 2-adrenoceptor stimulation induces locomotion in monoamine-depleted mice via a mechanism that may involve interference with glutamate receptor-mediated neurotransmission.
Carlsson
M L
ML
Department of Pharmacology, University of Göteborg, Sweden.
Engberg
G
G
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*
D015306:Biogenic Monoamines; D004338:Drug Combinations; D000431:Ethanol; D016202:N-Methylaspartate; D003000:Clonidine