Sensitization of gamma-aminobutyric acid-induced depressions of cerebellar Purkinje neurons to the potentiative effects of ethanol by beta adrenergic mechanisms in rat brain.
We previously reported that both systemic administration and brief local application of ethanol potentiated gamma-aminobutyric acid (GABA)-induced depressions of cerebellar Purkinje neurons when the GABA responses were concomitantly facilitated (modulated) by catecholaminergic agonists. In the present study, we further investigated the effects of prolonged local applications of ethanol, which more closely mimic the systemic application of ethanol, and we characterized the pharmacological specificity of the catecholaminergic interaction with these ethanol effects. As has been previously observed, iontophoretic applications of isoproterenol (ISO), a beta adrenergic agonist, facilitated GABA-induced depressions of cerebellar Purkinje neurons. The prolonged local application of ethanol produced a long-lasting potentiation of the ISO-modulated GABA responses that was similar in duration to that caused by systemic ethanol administration. The ethanol-induced augmentation of the ISO-modulated GABA responses was diminished both by terminating the beta adrenergic agonist application as well as by administering the beta adrenergic antagonist timolol. The alpha adrenergic agonist phenylephrine, on the other hand, either attenuated or had no effects on the GABA-induced depressions of cerebellar Purkinje neurons, and a subsequent application of ethanol did not potentiate GABA responses in the presence of phenylephrine. We conclude that prolonged local application of ethanol mimics the interaction of systemic ethanol with GABA-induced depressions of cerebellar Purkinje neurons. Furthermore, the catecholaminergic sensitization of GABA responses to these potentiative effects of ethanol is mediated by a beta adrenergic mechanism.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
A M
AM
Lin
R K
RK
Freund
M R
MR
Palmer
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D003864:Depression, Chemical; D000431:Ethanol / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D007545:Isoproterenol