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 loc al application of ethanol potentiated gamma-aminobutyric acid (GABA)-i nduced depressions of cerebellar Purkinje neurons when the GABA respon ses were concomitantly facilitated (modulated) by catecholaminergic ag onists. In the present study, we further investigated the effects of p rolonged local applications of ethanol, which more closely mimic the s ystemic application of ethanol, and we characterized the pharmacologic al 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-in duced 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 o f the ISO-modulated GABA responses was diminished both by terminating the beta adrenergic agonist application as well as by administering th e beta adrenergic antagonist timolol. The alpha adrenergic agonist phe nylephrine, on the other hand, either attenuated or had no effects on the GABA-induced depressions of cerebellar Purkinje neurons, and a sub sequent application of ethanol did not potentiate GABA responses in th e presence of phenylephrine. We conclude that prolonged local applicat ion of ethanol mimics the interaction of systemic ethanol with GABA-in duced depressions of cerebellar Purkinje neurons. Furthermore, the cat echolaminergic sensitization of GABA responses to these potentiative e ffects of ethanol is mediated by a beta adrenergic mechanism.