Opposite effects of two ligands for peripheral type benzodiazepine binding sites, PK 11195 and RO5-4864, in a conflict situation in the rat

Life Sci. 1985 Mar 18;36(11):1059-68. doi: 10.1016/0024-3205(85)90491-6.

Abstract

The effects of two drugs acting at the peripheral type benzodiazepine binding sites, PK 11195 and RO5-4864, were examined in shock-induced suppression of drinking in rats. These two compounds have opposite effects : RO5-4864 (3.1-1205 mg/kg i.p.) enhanced whereas PK 11195 (25-50 mg/kg i.p.) decreased the punished responding, and PK 11195 (6.25 mg/kg, a dose which did not alter the punished responding) blocked the proconflict action of RO5-4864 (6.25 and 12.5 mg/kg). The effects of RO5-4864 and PK 11195 were not antagonized by RO15-1788, a selective antagonist of the central benzodiazepine site. In addition, PK 11195 (6.25 mg/kg) did not reverse the proconflict effect of two beta-carbolines : beta-CEE and FG 7142. AS picrotoxin did not change the punished responding, these data imply that the effects of RO5-4864 and PK 11195 on the one hand and those of chlordiazepoxide and beta-carbolines on the other hand are differentially mediated and suggest that the peripheral type benzodiazepine binding sites are involved in this conflict model.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology*
  • Carbolines / pharmacology
  • Conditioning, Operant / drug effects
  • Conflict, Psychological*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electroshock
  • Flumazenil
  • Isoquinolines / pharmacology*
  • Ligands
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / drug effects*

Substances

  • Benzodiazepinones
  • Carbolines
  • Isoquinolines
  • Ligands
  • Receptors, GABA-A
  • 4'-chlorodiazepam
  • Flumazenil
  • FG 7142
  • beta-carboline-3-carboxylic acid ethyl ester
  • PK 11195