Effects of systemic and local ethanol on responses of rat cerebellar Purkinje neurons to iontophoretically applied γ-aminobutyric acid

Abstract

The goals of this study were: (1) to determine the effects of acute systemic or local application of ethanol (ETOH) on the response of cerebellar Purkinje cells (P-cells) to iontophoretically applied γ-aminobutyric acid (GABA) and (2) to characterize the effects of Ro15-4513, a putative antagonist of ETOH-GABA interactions, on ETOH-induced changes in GABA responsiveness. Male Sprague-Dawley rats (230–370 g) were anesthetized with halothane and implanted with intraperitoneal catheters for administration of ETOH (1.0–2.0 g/kg), before the recording session. Extracellular activity of single P-cells was recorded with the central barrel of a five-barrel micropipette, the other barrels of which were used for microiontophoresis of GABA and electro-osmosis of ETOH at the recording site. Spontaneous discharge and response of P-cells to GABA were monitored during a pre-ETOH control and for 1–1.5 h after systemic or electro-osmotic administration of ETOH. Transient suppression of spontaneous P-cell discharge was usually observed within 4–8 min of systemic ETOH injection. This effect lasted 2–4 min in 10 out of 19 rats tested. GABA-mediated inhibitory responses of cerebellar P-cells were increased by 45–50% relative to pre-ETOH values at 10 and 90 min post-ETOH injection. Prior administration of the imidazobenzodiazepine Ro15-4513 (4–6 mg/kg) failed to antagonize either the ETOH-induced enhancement of GABA-mediated inhibition o r the transient inhibition of spontaneous P-cell activity rat cerebellar P-cell produced by ETOH. In these studies, electro-osmotically applied ETOH produced a potent suppression of spontaneous P-cell activity which precluded further augmentation of unit responses to GABA. These results show that doses of systemically administered ETOH which are mildly intoxicating in the awake, behaving animal, enhance the inhibitory action of GABA on cerebellar P-cell discharge.