Research reportTonic modulatory role of mouse cerebellar α- and β-adrenergic receptors in the expression of ethanol-induced ataxia: Role of AC-cAMP

To further study neurochemical basis of ethanol-induced ataxia (EIA), we investigated role of cerebellar α and β-adrenergic receptors. Male CD-1 mice received intracerebellar microinfusion of adrenergic drugs to evaluate their effect on EIA (2 g/kg; ip) by Rotorod. Isoproterenol, phenylephrine (4, 8, 16 ng each), methoxamine (8 ng), and atenolol (2, 4, 8 ng), propranolol (4, 8, 16 ng), markedly attenuated and accentuated, respectively, EIA indicating the tonic nature of modulation. The attenuation of EIA by isoproterenol is β1-receptor mediated because it is blocked by atenolol. Tonic β1 modulation is functionally correlated with EIA potentiation by atenolol and propranolol. The prazosin-induced attenuation of EIA, initially thought of α1-receptor mediated, appeared instead β1-receptor modulated because of: (i) blockade by atenolol; and (ii) phosphodiesterase inhibition by prazosin. The phenylephrine/methoxamine-induced attenuation of EIA seems paradoxical as the response is similar to antagonist prazosin. However, functionally the attenuation seems β1 receptor-mediated since atenolol blocked it but prazosin did not. Also norepinephrine (NE) attenuated EIA that was inhibited by atenolol suggesting role of β1 receptors. Similarly yohimbine and rauwolscine attenuated EIA that indicates α2-receptor modulation associated with stimulation of AC-cAMP pathway. The results of study support the hypothesis that attenuation and potentiation of EIA is mediated by activation and inhibition of AC-cAMP pathway, respectively, in agreement with our previous reports, via direct and/or indirect activation of β-receptor.

► Isoproterenol reduced ethanol ataxia via β1-adrenergic receptor atenolol. ► Atenolol/propranolol accentuated ethanol ataxia via tonic β-adrenergic modulation. ► Phenylephrine/norepinephrine attenuated ethanol ataxia via α/β adrenergic receptors. ► Prazosin/rauwolscine/yohimbine reduce ethanol ataxia by phosphodiesterase inhibition.