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The Role of Nicotinic Acetylcholine Receptor (nAChR) α 7 Subtype in the Functional Interaction Between Nicotine and Ethanol in Mouse Cerebellum
Author(s) -
Taslim Najla,
Saeed Dar M.
Publication year - 2011
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.1530-0277.2010.01371.x
Subject(s) - nicotine , cerebellum , nicotinic acetylcholine receptor , acetylcholine receptor , nicotinic agonist , ethanol , chemistry , acetylcholine , neuroscience , pharmacology , receptor , biology , biochemistry
Background: Many epidemiological studies report that alcoholics overwhelmingly smoke tobacco and vice versa, which suggests a possible functional interaction between ethanol and nicotine. Although nicotine–ethanol interaction is well documented within the central nervous system, the mechanism is not well understood. Therefore, it is important from a public health standpoint to understand the mechanisms involved in nicotine and ethanol functional interaction. The intracerebellar (ICB) administration of nicotine significantly attenuates ethanol ataxia through nicotinic acetylcholine receptor (nAChR) α 4 β 2 subtype. This study, an extension of earlier work, was intended to investigate the possible role of nAChR subtype α 7 in mitigating ethanol ataxia. Methods: The effect of ICB injection of PNU‐282987 (α 7 agonist; 25 ng to 2.5 μg) and the antagonist methyllycaconitine was evaluated on ethanol (2 g/kg; i.p.)‐induced ataxia with a Rotorod. Cerebellar nitric oxide was determined fluorometrically in the presence of ethanol and/or PNU‐282987. Results: Attenuation of ethanol‐induced ataxia following PNU‐282987 microinfusion was dose‐dependent suggesting the participation of α 7 subtype in nicotine and ethanol interaction. Intracerebellar pretreatment with methyllycaconitine (α 7 ‐selective antagonist; 6 ng) virtually abolished the attenuating effect of PNU‐282987 as well as the effect of nicotine, but not of RJR‐2403 (α 4 β 2 ‐selective agonist; 125 ng) on ethanol‐induced ataxia. Finally, ethanol administration significantly decreased cerebellar NO x , whereas ICB PNU‐282987 significantly increased and/or opposed ethanol‐induced decrease in NO x . These results were functionally in agreement with our Rotorod data. Conclusions: These observations confirmed the following: (i) α 7 participation in nicotine–ethanol interaction and (ii) α 7 selectivity of methyllycaconitine. Overall, the results demonstrate the role of cerebellar nAChR α 7 subtype in nicotine‐induced attenuation of ethanol‐induced ataxia in cerebellar NO x ‐sensitive manner.