Premium
Mouse Cerebellar Adenosine‐Glutamate Interactions and Modulation of Ethanol‐Induced Motor Incoordination
Author(s) -
Dar M. Saeed
Publication year - 2002
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2002.tb02684.x
Subject(s) - glutamate receptor , nmda receptor , cerebellum , chemistry , adenosine , pharmacology , agonist , antagonist , ethanol , adenosine receptor , neuroscience , adenosine a1 receptor , adenosinergic , medicine , biochemistry , endocrinology , receptor , biology
Background It was demonstrated previously that cerebellar adenosine modulates ethanol‐induced motor incoordination via A 1 subtype of adenosine receptors. Several reports suggest the involvement of brain glutamate mechanisms, in particular N‐methyl‐d‐aspartate (NMDA) receptor sites, in the central nervous system (CNS) actions of ethanol. Mutually antagonistic functional responses as a result of glutamate and adenosine within the brain regions have also been well documented. Methods With the use of rotorod performance as the test response, this study was conducted to evaluate possible functional interactions between cerebellar adenosine and glutamate and its consequence on ethanol‐induced motor incoordination. Except for ethanol, which was injected intraperitoneally, all drugs used were microinfused directly into the cerebellum. Results Direct intracerebellar microinfusion of glutamate (125, 250, and 500 ng) and the antagonist l‐glutamic acid diethyl‐ester (125, 250, and 500 ng) markedly and dose‐dependently attenuated and accentuated, respectively, ethanol‐induced motor incoordination, suggesting an involvement of glutamate. Subsequently, intracerebellar microinfusions of NMDA (125, 250, and 500 ng) and its antagonists AP‐5 [(+)‐2‐amino‐5‐phosphoropentanoic acid; 125, 250, and 500 ng] and (+)‐MK‐801 [(+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a. d]‐cyclo‐hepten‐5,10‐imine hydrogen maleate; 25, 50, and 100 ng] significantly attenuated and accentuated, respectively, ethanol‐induced motor incoordination in a dose‐related manner, indicating participation of NMDA receptor. The attenuation of ethanol‐induced motor incoordination by glutamate and NMDA was receptor mediated as it was antagonized by their receptor antagonists. Adenosine A 1 ‐selective agonist N 6 ‐cyclohexyladenosine and antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine functionally opposed the attenuation by glutamate and NMDA and the accentuation by L‐glutamic acid diethyl‐ester, AP‐5, and (+)‐MK‐801, respectively, of ethanol‐induced motor incoordination. Conclusions These results suggest a functional antagonism between glutamate NMDA and adenosine A 1 receptors exhibiting a co‐modulation of ethanol‐induced motor incoordination within the cerebellum.