title: Differential effects of anxiogenic central and peripheral benzodiazepine receptor ligands in tests of learning and memory.
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.
authors.affiliation: Department of Psychology, Brown University, Providence, RI 02912.
authors.forename: P V
authors.initials: PV
authors.lastname: Holmes
authors.forename: R C
authors.initials: RC
authors.lastname: Drugan
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001362:Avoidance Learning / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D008024:Ligands; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D001570:Benzodiazepinones; D002243:Carbolines; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; C035874:FG 7142; C037850:PK 11195