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Involvement of κ‐Opioids in the Mouse Cerebellar Adenosinergic Modulation of Ethanol‐induced Motor Incoordination
Author(s) -
Dar M. Saeed
Publication year - 1998
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.1530-0277.1998.tb03672.x
Subject(s) - adenosinergic , chemistry , cerebellum , agonist , medicine , endocrinology , pharmacology , opioid , opioid receptor , receptor , antagonist , motor coordination , adenosine receptor , neuroscience , biochemistry , psychology
Using rotorod performance as the test response, possible modulation and co‐modulation of ethanol‐induced motor incoordination by the cerebellar κ‐opioid and adenosine A1 receptors was studied. A dose‐related accentuation of ethanol‐induced motor incoordination was observed after direct cerebellar microinfusion of three κ‐opioid receptor agonists: U‐50488, U‐62066, and bremazocine. On the contrary, significant and dose‐related attenuation of ethanol's motor impairment was produced by intracerebellar nor‐binaltorphimine, a κ‐opioid receptor antagonist. Furthermore, the accentuation by κ‐agonists was virtually abolished by κ‐antagonist nor‐binaltorphimine. Therefore, the accentuation and attenuation by κ‐opioid receptor agonists/antagonist, respectively, was through specific κ‐opioid receptors. Pretreatment with the intracerebellar adenosine A1‐selective agonist, N 6 ‐cyclohexyladenosine, further enhanced the ethanol‐induced motor incoordination and its accentuation by intracerebellar κ‐opioid receptor agonists. Ethanol‐induced motor incoordination was markedly attenuated by intracerebellar pertussis toxin (PTX) pretreatment, suggesting an involvement of PTX‐sensi‐tive G protein in the expression of motor incoordinating effect of ethanol. Additionally, the intracerebellar PTX also markedly attenuated the accentuation by κ‐opioid agonists of ethanol‐induced motor impairment, suggesting participation of PTX‐sensitive GTP‐binding G protein (G i , G o in the κ‐opioid modulation of ethanol's motor impairment. It also confirms that κ‐opioid receptors are linked to PTX‐sensitive G protein. The functional similarity between κ‐opioid and adenosine A1 receptors in increasing ethanol's motor incoordination, together with their anatomical co‐localization primarily on the axons and axonal terminals of the cerebellar granule cells, suggests a possible common catalytic unit of adenylate cyclase as the basis of modulation of ethanol‐induced motor incoordination by both receptor mechanisms.