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The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats.
Eur J Pharmacol. 2008 Nov 19; 598(1-3):57-63.EJ

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Pharmacodynamics, Medical University School, Lublin, Poland. jolka.kotlinska@am.lublin.plNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18838071

Citation

Kotlinska, Jolanta, and Marcin Bochenski. "The Influence of Various Glutamate Receptors Antagonists On Anxiety-like Effect of Ethanol Withdrawal in a Plus-maze Test in Rats." European Journal of Pharmacology, vol. 598, no. 1-3, 2008, pp. 57-63.
Kotlinska J, Bochenski M. The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats. Eur J Pharmacol. 2008;598(1-3):57-63.
Kotlinska, J., & Bochenski, M. (2008). The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats. European Journal of Pharmacology, 598(1-3), 57-63. https://doi.org/10.1016/j.ejphar.2008.09.026
Kotlinska J, Bochenski M. The Influence of Various Glutamate Receptors Antagonists On Anxiety-like Effect of Ethanol Withdrawal in a Plus-maze Test in Rats. Eur J Pharmacol. 2008 Nov 19;598(1-3):57-63. PubMed PMID: 18838071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats. AU - Kotlinska,Jolanta, AU - Bochenski,Marcin, Y1 - 2008/09/27/ PY - 2008/04/24/received PY - 2008/09/05/revised PY - 2008/09/18/accepted PY - 2008/10/8/pubmed PY - 2009/1/10/medline PY - 2008/10/8/entrez SP - 57 EP - 63 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 598 IS - 1-3 N2 - 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18838071/The_influence_of_various_glutamate_receptors_antagonists_on_anxiety_like_effect_of_ethanol_withdrawal_in_a_plus_maze_test_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00970-9 DB - PRIME DP - Unbound Medicine ER -