Potentiation of ethanol effects in cerebellum by activation of endogenous noradrenergic inputs

We previously found that beta adrenergic agonists such as norepinephrine an d isoproterenol potentiate the depressant actions of ethanol (ROH) on cereb ellar Purkinje neurons. Furthermore, antagonism of the beta adrenergic effe cts of endogenously released catecholamines with timolol reduced EtOH-induc ed depressions of neuronal activity in that brain area. In the present stud y, we further investigated the hypothesis that activity of the endogenous n oradrenergic innervation to the cerebellar cortex can potentiate this EtOH action. We investigated the interaction of synaptically released catecholam ines on EtOH-induced depressions of cerebellar Purkinje neurons in three di fferent experiments: (1) endogenous catecholamine release was facilitated b y applying the catecholamine uptake inhibitor desmethylimipramine, (2) acti vity of the noradrenergic innervation of the cerebellar cortex from locus c eruleus was increased by causing acute withdrawal from 7 days of chronic mo rphine treatment with the opiate antagonist naloxone, and (3) the noradrene rgic innervation of the cerebellum was activated directly by electrical sti mulation of the locus ceruleus. We found that all three conditions potentia ted EtOH-induced depressions in the cerebellum and that this potentiation o f ethanol effects could be antagonized by the systemic administration of th e beta adrenergic antagonist propranolol. Furthermore, morphine withdrawal also caused potentiation of the depressant effects of phencyclidine, which are known to be regulated by the endogenous catecholamine innervation in th is brain area. Taken together with our previous data demonstrating a beta a drenergic facilitation of EtOH actions in this brain area, the present resu lts suggest that the activity of endogenous noradrenergic synapses can regu late the depressant effects of ROH on cerebellar Purkinje neurons.