title: Effects of systemic and local ethanol on responses of rat cerebellar Purkinje neurons to iontophoretically applied norepinephrine and gamma-aminobutyric acid.
abstract: The goal of the present study was to determine the effect of acute ethanol (ETOH), administered intraperitoneally or electro-osmotically, on norepinephrine (NE) induced increases in gamma-aminobutyric acid (GABA) mediated inhibition of single cerebellar Purkinje neurons (P-cells). Male Sprague-Dawley rats (230-370g) were anesthetized with halothane and implanted with an intraperitoneal catheter for systemic administration of ETOH (1.0-1.5 g/kg) prior to the recording session. Extracellular activity of single P-cells was recorded before and after iontophoresis of GABA and NE using five-barrel glass micropipettes. GABA was administered at the recording site by microiontophoretic pulses before, during and after continuous iontophoretic application of NE. Spontaneous discharge, GABA responses and NE-GABA interactions in P-cells were monitored for each experiment before and 1-1.5 h following systemic administration of ETOH. As in our previous reports administration of NE, at low ejection currents (10-60 nA), augmented GABA mediated suppression of P-cell spontaneous discharge. Between 10 and 60 min after injection of ETOH, this NE induced augmentation of GABA inhibition was further potentiated. This potentiation involved increases in both the magnitude and the duration of the GABA inhibition observed after NE alone. NE-induced augmentation of GABA inhibition persisted for 2-13 min longer after ETOH administration than in the pre-ETOH control period. Local electro-osmotic application of ETOH, which resulted in strong depression of spontaneous activity and caused small increases in GABA-mediated inhibition, did not directly potentiate NE-induced augmentation of GABA action. These results indicate that NE-mediated augmentation of GABA inhibition of P-cell activity is potentiated following systemic, but not local, ETOH administration.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Lee
authors.forename: S S
authors.initials: SS
authors.lastname: Smith
authors.forename: J K
authors.initials: JK
authors.lastname: Chapin
authors.forename: N
authors.initials: N
authors.lastname: Shimizu
authors.forename: B D
authors.initials: BD
authors.lastname: Waterhouse
authors.forename: B N
authors.initials: BN
authors.lastname: Maddus
authors.forename: D J
authors.initials: DJ
authors.lastname: Woodward
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004357:Drug Synergism; D004594:Electrophysiology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007478:Iontophoresis; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001386:Azides; D002492:Central Nervous System Depressants; D013566:Sympathomimetics; D001569:Benzodiazepines; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C042957:Ro 15-4513; D009638:Norepinephrine