Tobacco Science SITAB 21_2011

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) α4β2 subtype. This study, an extension of earlier work, was intended to investigate the possible role of nAChR subtype α7 in mitigating ethanol ataxia. Methods: The effect of ICB injection of PNU-282987 (α7 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 α7 subtype in nicotine and ethanol interaction. Intracerebellar pretreatment with methyllycaconitine (α7-selective antagonist; 6 ng) virtually abolished the attenuating effect of PNU282987 as well as the effect of nicotine, but not of RJR-2403 (α4β2-selective agonist; 125 ng) on ethanolinduced ataxia. Finally, ethanol administration significantly decreased cerebellar NOx, whereas ICB PNU282987 significantly increased and/or opposed ethanol-induced decrease in NOx. These results were functionally in agreement with our Rotorod data. Conclusions: These observations confirmed the following: (i) α7 participation in nicotine ethanol interaction and (ii) α7 selectivity of methyllycaconitine. Overall, the results demonstrate the role of cerebellar nAChR α7 subtype in nicotine-induced attenuation of ethanol-induced ataxia in cerebellar NOx-sensitive manner. http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2010.... Tobacco Science Globalink Medical Journal Update N. 21 2 marzo 2011 Editor: Giacomo Mangiaracina. Editorial board: Massimo Baraldo, Fabio Beatrice, Cristiano Chiamulera, Mario del Donno, Domenico Enea, Nolita Pulerà, Biagio Tinghino, Vincenzo Zagà. Newsletter of The Italian Society of Tobaccology www.tabaccologia.org 21 2011