Noradrenaline modulates neuronal responses to GABA in vestibular nuclei

Abstract: The effects of noradrenaline (NA) on the inhibitory responses to GABA were studied in vivo in neurons of the vestibular nuclei of the rat using extracellular recordings of single unit electrical activity and a microiontophoretic technique of drug application in loco. NA application influenced GABA-evoked inhibitions in 82% of tested neurons, depressing them in 42% and enhancing them in 40% of cases. The more frequent action of NA on GABA responses was depressive in lateral and superior vestibular nuclei (50% of neurons) and enhancing in the remaining nuclei (56% of neurons). The most intense effect of NA application was the enhancement of GABA responses induced in a population of lateral vestibular nucleus neurons, characterized by a background firing rate significantly higher than that of other units. The alpha2 noradrenergic receptor agonist clonidine mimicked the enhancing action of NA on GABA responses; this action was blocked by application of the specific alpha2 antagonist yohimbine. The beta adrenergic agonist isoproterenol induced either depressive or enhancing effects on GABA responses; the former more than the latter were totally or partially blocked by application of the beta antagonist timolol. It is concluded that NA enhances GABA responses by acting on noradrenergic alpha2 and to a lesser extent beta receptors, whereas depressive action involves beta receptors only. These results confirm the hypothesis that the noradrenergic system participates in the regulation of the vestibulospinal and the vestibulo-ocular reflexes and suggest that conspicuous changes of NA content in brain due to aging or stress could lead to a deterioration in the mechanisms of normal vestibular function. [Copyright &y& Elsevier]