Dual action of the benzodiazepine receptor inverse agonist RU34347 on responses to exogenously applied GABA in the rat cerebellar slice.
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.
Pringle
A K
AK
Department of Physiology and Pharmacology, School of Biological Sciences, University of Southampton, UK.
Gardner
C R
CR
Walker
R J
RJ
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*
D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D007093:Imidazoles; D011743:Pyrimidines; C102746:RU 34347; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid