The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats.
The aim of the present study was to determine whether various glutamate receptor antagonists could affect ethanol withdrawal-induced anxiety-like behavior measured in the elevated plus-maze test in rats. In our study, memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, did not show any effect on ethanol withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate5 (mGlu5) receptor antagonist), at a dose of 400 mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and open arms entries. Antagonists of group I mGlu receptors, such as MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine, mGlu5 receptor) or EMQMCM (3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate, mGlu1 receptor), caused similar effects to acamprosate. In contrast to acamprosate and MTEP, EMQMCM (5 mg/kg) elevated the ethanol withdrawal-induced decrease in locomotion. When given alone to the saline-treated group, EMQMCM indicated anxiolytic-like effect. Our results imply a crucial role of mGlu5 receptor in an anxiety-like effect of ethanol withdrawal because MTEP (a selective mGlu5 receptor antagonist) and acamprosate (which also indirectly inhibits mGlu5 receptor) attenuated ethanol withdrawal anxiety-like behavior without influence on ethanol withdrawal hypolocomotion and did not show any effect in the saline-treated groups. However, difference in anxiolytic-like potency between both these group I mGlu receptors antagonists may be due to the recent experimental design. Therefore, taking into account a positive correlation between ethanol withdrawal-induced anxiety and relapse to ethanol drinking, our results suggest that mGlu receptor antagonists of group I (similarly to acamprosate) could prevent relapse to drinking and, therefore they might be useful in therapy of alcoholism.
Kotlinska
Jolanta
J
Department of Pharmacology and Pharmacodynamics, Medical University School, Lublin, Poland. jolka.kotlinska@am.lublin.pl
Bochenski
Marcin
M
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D017470:Receptors, Glutamate / Q000187:drug effects*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
C502015:(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate; D008559:Memantine