| First Author | Taslim N | Year | 2011 |
| Journal | Behav Brain Res | Volume | 217 |
| Issue | 2 | Pages | 282-92 |
| PubMed ID | 20974182 | Mgi Jnum | J:167558 |
| Mgi Id | MGI:4868541 | Doi | 10.1016/j.bbr.2010.10.026 |
| Citation | Taslim N, et al. (2011) Role of mouse cerebellar nicotinic acetylcholine receptor (nAChR) alpha(4)beta(2)- and alpha(7) subtypes in the behavioral cross-tolerance between nicotine and ethanol-induced ataxia. Behav Brain Res 217(2):282-92 |
| abstractText | We have demonstrated that nicotine attenuated ethanol-induced ataxia via nicotinic-acetylcholine-receptor (nAChR) subtypes alpha(4)beta(2) and alpha(7). In the present study, ethanol (2g/kg; i.p.)-induced ataxia was assessed by Rotorod performance following repeated intracerebellar infusion of alpha(4)beta(2)- and alpha(7)-selective agonists. Localization of alpha(4)beta(2) and alpha(7) nAChRs was confirmed immunohistochemically. Cerebellar NO(x) (nitrite+nitrate) was determined flurometrically. Repeated intracerebellar microinfusion of the alpha(4)beta(2)-selective agonist, RJR-2403 (for 1, 2, 3, 5 or 7 days) or the alpha(7)-selective agonist, PNU-282987 (1, 2, 3 or 5 days), dose-dependently attenuated ethanol-induced ataxia. These results suggest the development of cross-tolerance between ethanol-induced ataxia and alpha(4)beta(2) and alpha(7) nAChR agonists. With RJR-2403, the cross-tolerance was maximal after a 5-day treatment and lasted 48h. Cross-tolerance was maximal after a 1-day treatment with PNU-282987 and lasted 72h. Pretreatment with alpha(4)beta(2)- and alpha(7)-selective antagonists, dihydro-beta-erythroidine and methyllycaconitine, respectively, prevented the development of cross-tolerance confirming alpha(4)beta(2) and alpha(7) involvement. Repeated agonist infusions elevated cerebellar NO(x) 16h after the last treatment while acute ethanol exposure decreased it. Pretreatment with repeated RJR-2403 or PNU-282987 reversed ethanol-induced decrease in NOx. The NO(x) data suggests the involvement of the nitric oxide (NO)-cGMP signaling pathway in the cross-tolerance that develops between alpha(4)beta(2)- and alpha(7)-selective agonists and ethanol ataxia. Both alpha(4)beta(2) and alpha(7) subtypes exhibited high immunoreactivity in Purkinje but sparse expression in molecular and granular cell layers. Our results support a role for alpha(4)beta(2) and alpha(7) nAChR subtypes in the development of cross-tolerance between nicotine and ethanol with the NO signaling pathway as a potential mechanism. |
