Functional Role for Mouse Cerebellar NO /c GMP / K (ATP) Pathway in Ethanol‐Induced Ataxia

Background We have previously shown that brain adenosine A 1 receptors and nitric oxide ( NO ) play an important role in ethanol ( E t OH )‐induced cerebellar ataxia ( EICA ) through glutamate/ NO /c GMP pathway. I now report possible modulation of EICA by the cerebellar NO /c GMP / K (ATP) pathway. Methods EICA was evaluated by R otorod in CD ‐1 male mice. All drugs ( K (ATP) activators pinacidil, 0.05, 0.1, 0.5 nmol; minoxidil, 0.01, 0.1, 1.0 pmol; antagonists glipizide/glibenclamide, 0.01, 0.05, 0.1 nmol; NO donor l ‐arginine, 20 nmol; NOS inhibitors [ iNOS ] inhibitor L‐NAME , 50 nmol; glutamate, 1.5 nmol; adenosine A 1 receptor agonist N 6 ‐cyclohexyladenosine [ CHA ], 6, 12 pmol; antagonist DPCPX , 0.1 or 0.4 nmol) were given by direct intracerebellar microinfusion via stereotaxically implanted guide cannulas, except E t OH (2 g/kg, i.p.). Results Pinacidil and minoxidil dose‐dependently accentuated, whereas glipizide and glibenclamide markedly attenuated EICA , indicating tonic participation of K (ATP) channels. Glipizide abolished the pinacidil potentiation of EICA , which confirmed both drugs acted via K (ATP) channels. A possible link between K (ATP) channels and glutamate/ NO pathway was suggested when (i) CHA (12 pmol) totally abolished l ‐arginine‐induced attenuation of EICA ; (ii) L‐NAME abolished l ‐arginine‐induced attenuation of EICA associated with further increase in EICA ; and (iii) the combined l ‐arginine and glutamate infusion virtually abolished EICA . Also, whereas CHA abolished glibenclamide‐induced attenuation and potentiated pinacidil/minoxidil‐induced accentuation of EICA , the effects of DPCPX were just the opposite to those of CHA . Conclusions The results with CHA therefore suggest a functional link between K (ATP) and A 1 receptors and between K (ATP) and glutamate/ NO and as an extension may involve participation of NO /c GMP / K (ATP) pathway in EICA .