title: Dual action of the benzodiazepine receptor inverse agonist RU34347 on responses to exogenously applied GABA in the rat cerebellar slice.
abstract: The benzodiazepine receptor inverse agonist has been shown to produce agonist-like effects at low concentrations. RU34347 has both inverse agonist (attenuation of GABA-responses) and agonist-like (reduction of spontaneous Purkinje cell firing rate) in the cerebellar slice preparation. The benzodiazepine antagonist flumazenil prevented the inverse agonist actions, but only partially reduced the agonist-like effects. Further, brief application of RU34347 to slices mimicked the response to GABA, and pharmacological investigation determined that this action was mediated through increased GABA through action at a site proximal to the parallel fiber-basket cell synapse, at an as yet undetermined receptor.
authors.affiliation: Department of Physiology and Pharmacology, School of Biological Sciences, University of Southampton, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Pringle
authors.forename: C R
authors.initials: CR
authors.lastname: Gardner
authors.forename: R J
authors.initials: RJ
authors.lastname: Walker
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D007093:Imidazoles; D011743:Pyrimidines; C102746:RU 34347; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid