Modulation of GABA-mediated inhibition in rat cerebellar slices by benzodiazepine receptor ligands.
1. Extracellular recordings were made from the Purkinje cell layer of rat cerebellar slices. Compounds were perfused over the slice and bipolar stimulating electrodes placed in the external layer of the slice close to the recording electrode. 2. Stimulus-evoked inhibition of Purkinje layer cell activity was sensitive to bicuculline methiodide and picrotoxin, suggesting it was gamma-aminobutyric acid (GABA) mediated. The benzodiazepine ligands RU 32007 and Ro 19-0528 reversibly increased the period of inhibition, as did pentobarbital. This benzodiazepine effect was antagonised by Ro 15-1788. 3. Five inverse agonists all reduced the period of stimulated inhibition and this effect was reversed by Ro 15-1788, suggesting the involvement of benzodiazepine receptors. 4. It is concluded that this system provides a convenient physiological and possibly quantitative model for studying the action of benzodiazepine receptor ligands.
Hussain
S
S
Department of Physiology and Pharmacology, School of Biological Sciences, University of Southampton, England.
Bagust
J
J
Ward
R A
RA
Gardner
C R
CR
Walker
R J
RJ
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects*; D004558:Electric Stimulation; D004566:Electrodes; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D001640:Bicuculline; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid