PT  - JOURNAL ARTICLE
AU  - Basile, A S
AU  - Bolger, G T
AU  - Lueddens, H W
AU  - Skolnick, P
TI  - Electrophysiological actions of Ro5-4864 on cerebellar Purkinje neurons: evidence for "peripheral" benzodiazepine receptor-mediated depression.
DP  - 1989 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 463--469
VI  - 248
IP  - 1
4099  - http://jpet.aspetjournals.org/content/248/1/463.short
4100  - http://jpet.aspetjournals.org/content/248/1/463.full
SO  - J Pharmacol Exp Ther1989 Jan 01; 248
AB  - The effects of Ro 5-4864 (4'-chlorodiazepam; the archetypic peripheral benzodiazepine receptor ligand) were examined on the electrophysiological responses of rat cerebellar Purkinje neurons maintained in vitro. Ro 5-4864 produced a biphasic response (consisting of an increase followed by a decrease in spontaneous firing) in approximately 50% of the neurons studied. The remaining neurons responded to Ro 5-4864 application with decreased spontaneous activity. The EC50 and IC50 values for the excitatory and depressant responses to Ro 5-4864 were 490 and 450 nM, respectively. Preincubation with PK 11195 [N-methyl-N-(methyl-1-propyl)chloro-2-phenyl-1-isoquinoline-3-carboxamid e; a peripheral benzodiazepine receptor antagonist] reduced the potency of Ro 5-4864 to inhibit cell firing in a competitive fashion, but did not alter Ro 5-4864-elicited excitations. A similar effect was observed with the monocarboxylic acid anion transport inhibitor UK 5099 [alpha-cyano-beta-(1-phenylindol-3-yl)acrylate]. In contrast, the increases in cell firing elicited by t-butylbicyclophosphorothionate (a GABA-gated chloride channel blocker) were enhanced 6-fold by coperfusion with both Ro 5-4864 and PK 11195. These findings suggest that the Ro 5-4864 induced depressions of Purkinje neuron spontaneous activity is mediated by peripheral benzodiazepine receptors, whereas the excitation may result from modulation of the gamma-aminobutyric acid-gated chloride ionophore.