title: The role of nicotinic acetylcholine receptor (nAChR) α7 subtype in the functional interaction between nicotine and ethanol in mouse cerebellum.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
authors.forename: Najla
authors.initials: N
authors.lastname: Taslim
authors.forename: M
authors.initials: M
authors.lastname: Saeed Dar
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D001549:Benzamides / Q000008:administration & dosage; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009538:Nicotine / Q000008:administration & dosage*; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001549:Benzamides; D001643:Bridged Bicyclo Compounds; C579166:Chrna7 protein, mouse; C498513:PNU-282987; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D000431:Ethanol; D009538:Nicotine; D000157:Aconitine