title: Absence of repeated-trial tolerance to the anxiolytic-like effects of chlordiazepoxide in the rat triple test.
abstract: The triple test, recently developed to assess anxiety-related behaviors in rodents, combines three widely used behavioral tests: the open field (OF), elevated plus maze (EPM) and light/dark box (LDB). The EPM and LDB, individually, are normally sensitive to the anxiolytic effects of benzodiazepines only in the first trial, due to the phenomenon of one-trial tolerance, which limits their use in longitudinal studies. The main objective of the present investigation was to verify whether the anxiolytic-like effects of chlordiazepoxide (CDZ), previously observed in naive animals submitted to the triple test, would persist after repeated testing. To this end, three experiments were carried out where male Wistar rats received CDZ (10mg/kg) 30min before the triple test for 2, 3 or 20 consecutive days. Except for the first day of drug treatment following a previous test experience in an undrugged state, CDZ had enduring anxiolytic-like effects under all schedules, promoting an increase in the exploration of the EPM open arms (and in some cases of the white compartment of the LDB), without affecting the number of closed-arm entries. The finding that rats did not develop tolerance to CDZ even with chronic treatment and repeated exposures to the triple test suggests that this new device is a promising tool to be used in longitudinal studies involving pharmacological manipulations of anxiety-related behaviors.
authors.affiliation: Laboratório de Genética do Comportamento, Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, 88.040-900, Florianópolis, SC, Brazil.
authors.forename: Thaize D
authors.initials: TD
authors.lastname: Wehrmeister
authors.forename: Geison S
authors.initials: GS
authors.lastname: Izídio
authors.forename: Elayne
authors.initials: E
authors.lastname: Pereira
authors.forename: Gustavo
authors.initials: G
authors.lastname: Izídio
authors.forename: André
authors.initials: A
authors.lastname: Ramos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology*; D004361:Drug Tolerance; D005106:Exploratory Behavior / Q000187:drug effects; D008027:Light; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014151:Anti-Anxiety Agents; D002707:Chlordiazepoxide