Ethanol-induced depressions of cerebellar Purkinje neurons are potentiated by beta-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 GABAA mechanism. These neurons receive a prominent noradrenergic input from the locus coeruleus. Stimulation of the locus coeruleus or local application of beta-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 beta-adrenergic agonist isoproterenol potentiated EtOH-induced depressions of Purkinje neuron firing. This isoproterenol interaction with EtOH was antagonized by the beta-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 involved endogenous GABA actions that may be regulated by beta-adrenergic mechanisms.
Lin
A M
AM
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
Freund
R K
RK
Hoffer
B J
BJ
Palmer
M R
MR
D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D007545:Isoproterenol