Ethanol-induced depressions of cerebellar Purkinje neurons are potentiated by β-adrenergic mechanisms in rat brain

Electrophysiological studies indicate that EtOH decreases the firing rate of cerebellar Purkinje neurons in vivo and in vitro through a GABA(A) mechanism. These neurons receive a prominent noradrenergic input from the locus coeruleus. Stimulation of the locus coeruleus or local application of β-adrenergic agonists potentiates Purkinje neuron responses to GABA and sensitizes GABA responses to the potentiative effects of EtOH. In the present study, we found that the modulatory influences of the β-adrenergic agonist isoproterenol potentiated EtOH-induced depressions of Purkinje neuron firing. This isoproterenol interaction with EtOH was antagonized by the β-adrenergic antagonist timolol. We found evidence that endogenous catecholamines can cause this effect as well. Timolol antagonized EtOH-induced depressions on 20% of the neurons studied. This was the same frequency as that previously found for EtOH-induced potentiations of GABA depressions in this brain area. These data suggest that the Purkinje neurons showing this interaction receive spontaneously active catecholamine inputs that sensitize the GABA effects to the potentiative effects of ethanol. Consistent with this hypothesis, we also found that timolol antagonized this GABA/EtOH interaction. Taken together, these results are consistent with the hypothesis that EtOH-induced depressions of Purkinje neurons involve endogenous GABA actions that may be regulated by β-adrenergic mechanisms.