ACTION OF ETHANOL AND ZOLPIDEM ON GAMMA-AMINOBUTYRIC-ACID RESPONSES FROM CEREBELLAR PURKINJE NEURONS - RELATIONSHIP TO BETA-ADRENERGIC-RECEPTOR INPUT

The observation that cerebellar Purkinje cells contain type-I benzodia zepine-sensitive GABA(A) receptors is consistent with findings in the present work that the majority of Purkinje neurons are sensitive to en hancement of GABA by the type-1 benzodiazepine agonist, zolpidem. Prev ious work has demonstrated a relation between zolpidem and ethanol enh ancement of GABA responses in several brain regions, but had not teste d Purkinje neurons. Therefore, given that a majority of Purkinje neuro ns were found to be sensitive to zolpidem, ethanol would have been exp ected to enhance GABA responses from this cell type. However, in agree ment with earlier electrophysiological studies, ethanol enhanced GABA inhibitory responses from only a small proportion of these cerebellar Purkinje neurons. Rather than enhancement of GABA, local application o f ethanol either inhibited or did not affect responses to GABA from a majority of cerebellar-Purkinje neurons. Nonetheless, as previously re ported, a portion of the Purkinje neurons initially insensitive to eth anol enhancement of GABA became sensitive to this action of ethanol wi th co-application of the beta-adrenergic agonist, isoproterenol. Thus, these results collectively implicate a beta-adrenergic input dependen cy for ethanol enhancement of GABA from some, but not all, cerebellar Purkinje neurons sensitive to zolpidem. Because a beta-adrenergic inpu t did not allow ethanol enhancement of GABA from all Purkinje neurons, future studies should explore the possibility that other auxiliary ne ural inputs to zolpidem-sensitive cerebellar Purkinje neurons may be r equired for ethanol enhancement of GABA responsiveness when a beta-adr energic input does not have this action. Likewise, knowing that the ac tion of zolpidem can predict ethanol enhancement of GABA in other brai n regions, the present findings suggest that a future determination be made concerning whether zolpidem-sensitive neurons in these other reg ions of brain require a beta-adrenergic or an alternative neural input for ethanol enhancement of GABA responses.