Differential effects of anxiogenic central and peripheral benzodiazepine receptor ligands in tests of learning and memory

Psychopharmacology (Berl). 1991;104(2):249-54. doi: 10.1007/BF02244187.

Abstract

Previous research has demonstrated that low doses of anxiogenic central benzodiazepine receptor (CBR) ligands, the beta-carbolines, improve performance in various learning and memory tests in animals if administered prior to training. The present experiments compared the effect of a beta-carboline (FG 7142) with that of a pharmacologically distinct anxiogenic compound, a peripheral benzodiazepine receptor (PBR) ligand, 4'-chlorodiazepam (Ro5-4864), in two tests of learning and memory in rats. As expected, FG 7142 significantly improved performance in a passive avoidance test. Ro5-4864 was without effect. In a shuttlebox escape test, Ro5-4864 significantly impaired performance while FG 7142 had no effect. The effect of Ro5-4864 was antagonized by the specific peripheral benzodiazepine receptor antagonist, PK 11195. These results indicate that the differential impact of CBR and PBR anxiogenic ligands on performance in aversively-motivated learning tests may be a reflection of their distinct pharmacologies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anxiety / psychology*
  • Avoidance Learning / drug effects
  • Benzodiazepinones / pharmacology
  • Carbolines / pharmacology
  • Conditioning, Operant / drug effects
  • Isoquinolines / pharmacology
  • Learning / drug effects*
  • Ligands
  • Male
  • Memory / drug effects*
  • Rats
  • Rats, Inbred Strains
  • Reaction Time / drug effects
  • Receptors, GABA-A / drug effects*

Substances

  • Benzodiazepinones
  • Carbolines
  • Isoquinolines
  • Ligands
  • Receptors, GABA-A
  • 4'-chlorodiazepam
  • FG 7142
  • PK 11195