Ethanol modulation of gamma-aminobutyric acid (GABA)-mediated inhibition of cerebellar Purkinje neurons: Relationship to GABA(b) receptor input

Background: Electrophysiological recording reveals that only a portion of c erebellar Purkinje neurons are sensitive to ethanol enhancement of gamma-am inobutyric acid (GABA) responses. Although activation of beta-adrenergic re ceptors permits ethanol enhancement of GABA function from some cerebellar P urkinje neurons, other neurons remain insensitive to ethanol. These finding s are consistent with the finding that other external neural inputs are req uired to allow ethanol enhancement of GABA responses from Purkinje neurons. Because of a high expression of GABA(B) receptors on Purkinje cells, we te sted whether activation of GABA(B) receptors might modulate the action of e thanol on GABA responsiveness. Methods: Extracellular single-unit electrophysiological recording was used to investigate the effects of ethanol on responses to GABA and muscimol (a GABA(A) agonist) from cerebellar Purkinje neurons. Drugs tested were baclop hen (a GABA(B) agonist) and CGP35348 (a GABA(B) antagonist). Results: Ethanol did not enhance responses to GABA and muscimol from all Pu rkinje neurons. Systemic administration of the GABA(B) agonist, baclophen ( 3 mg/kg intravenously), permitted ethanol to enhance GABA inhibition from s imilar to 75% of cerebellar Purkinje neurons not initially enhanced by etha nol. Local iontophoretic application of baclophen to Purkinje neurons also allowed ethanol to enhance GABA and muscimol responsiveness from a portion of neurons in which ethanol initially did not affect their actions. An inhi bitory action of ethanol on responses to GABA and muscimol, which was also influenced by baclophen, was observed from some Purkinje neurons. From Purk inje neurons initially sensitive to ethanol enhancement of GABA and muscimo l function, administration of CGP35348, a GABA(B) antagonist, diminished th e effect of ethanol on the responsiveness of these agonists from the majori ty (9/15) of neurons. Conclusions: The present findings demonstrated that baclophen allows ethano l enhancement of GABA and muscimol responsiveness from some, but not all, c erebellar Purkinje neurons initially not sensitive to ethanol. Likewise, a GABA(B) antagonist can diminish ethanol enhancement of GABA and muscimol re sponses from some ethanol-sensitive neurons. Thus, these results emphasize that GABA(B) receptors on a portion of Purkinje neurons act as an auxiliary neural input that allows ethanol enhancement of GABA responses. Consequent ly, receptor structure alone does not account for the action of ethanol on GABA(A) receptor function on this cell type.