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

M Saeed Dar, Salim Al-Rejaie

Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. darm@ecu.edu

Behavioural brain research 2013 Mar 15


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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 (2g/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 β(1)-receptor mediated because it is blocked by atenolol. Tonic β(1) modulation is functionally correlated with EIA potentiation by atenolol and propranolol. The prazosin-induced attenuation of EIA, initially thought of α(1)-receptor mediated, appeared instead β(1)-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 β(1) receptor-mediated since atenolol blocked it but prazosin did not. Also norepinephrine (NE) attenuated EIA that was inhibited by atenolol suggesting role of β(1) receptors. Similarly yohimbine and rauwolscine attenuated EIA that indicates α(2)-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. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

M Saeed Dar, Salim Al-Rejaie. Tonic modulatory role of mouse cerebellar α- and β-adrenergic receptors in the expression of ethanol-induced ataxia: role of AC-cAMP. Behavioural brain research. 2013 Mar 15;241:154-60

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PMID: 23246526

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