title: Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test.
abstract: This study examined the effects of peripheral-type benzodiazepine receptors in the forced swimming test. PK 11195 (1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-isoquinoline carboxamide) and Ro5-4864 (7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine-2-one) were i.p. injected in mice, according to an acute (1 or 24 h) and a repeated (14 days) schedule. Pretreatment with the agonist, Ro5-4864, significantly reduced immobility time 1 h after treatment but not 24 h after it, whereas the antagonist, PK11195, did not interfere with the test parameters. Nevertheless, PK11195 pretreatment inhibited the Ro5-4864 antidepressant-like effect. Animals repeatedly treated with Ro5-4864 had a similar profile of action with no sign of motor impairment or locomotor activation as evaluated in the rota-rod and open-field tests, respectively. Aminoglutethimide pretreatment, which blocks the early step of steroid synthesis, inhibited the antidepressant-like effect of Ro5-4864. The present findings suggest an antidepressant-like profile for the benzodiazepine, Ro5-4864, that seems to involve steroid synthesis as underlying mechanism.
authors.affiliation: Department of Pharmacology, Center of Biological Science, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82- Centro, 88015-420 Florianópolis SC, Brazil.
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Gavioli
authors.forename: Filipe Silveira
authors.initials: FS
authors.lastname: Duarte
authors.forename: Elizangela
authors.initials: E
authors.lastname: Bressan
authors.forename: Pascual
authors.initials: P
authors.lastname: Ferrara
authors.forename: Roseli Coimbra
authors.initials: RC
authors.lastname: Farges
authors.forename: Thereza Christina Monteiro
authors.initials: TC
authors.lastname: De Lima
mesh_terms: D000616:Aminoglutethimide / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058785:GABA-A Receptor Agonists; D007099:Imipramine / Q000008:administration & dosage / Q000493:pharmacokinetics; D007103:Immobilization; D007274:Injections, Intraperitoneal; D007546:Isoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017933:Peripheral Nervous System / Q000737:chemistry; D011963:Receptors, GABA-A / Q000187:drug effects*; D045442:Rotarod Performance Test; D013550:Swimming; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D001570:Benzodiazepinones; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D011963:Receptors, GABA-A; D000616:Aminoglutethimide; D001569:Benzodiazepines; C028513:4'-chlorodiazepam; D007099:Imipramine; C037850:PK 11195