title: Evaluation of the effect of acute sibutramine in female rats in the elevated T-maze and elevated plus-maze tests.
abstract: Sibutramine is a serotonin and norepinephrine reuptake inhibitor indicated for the treatment of obesity. A pre-clinical study showed that acute administration of sibutramine promoted anxiolytic- and panicolytic-like effects in male rats. However, in clinical reports, sibutramine favoured the onset of panic attacks in women. In this study, the effect of sibutramine on experimental anxiety in females and the relevance of different oestrous cycle phases for this effect were analysed. In experiment 1, both male and female rats were submitted to acute intraperitoneal injection of sibutramine or vehicle 30 min. before testing in the elevated T-maze (ETM) and in the open-field test (OF). Females in the pro-oestrus (P), oestrus (E), early dioestrus (ED) and late dioestrus (LD) phases were tested in the ETM and OF (experiment 2) or in the elevated plus-maze (EPM) 30 min. after the injection of sibutramine. Sibutramine impaired the escape response in the ETM in both males and females. This effect was observed for P, E and ED, but not for LD females. Sibutramine altered neither the inhibitory avoidance in the ETM nor the behaviour of females in the EPM. Thus, sibutramine promoted a panicolytic-like effect in female rats cycling at P, E and ED, but not in the LD phase and did not alter behaviours related to anxiety in both ETM and EPM. Considering that pre-clinical studies aiming the screening of anxiolytic drugs employ male rodents, data here obtained reinforce the importance of better understanding the effects of drugs in females.
authors.affiliation: Laboratory of Behavioural Pharmacology, Department of Biophysics and Pharmacology, Biosciences Center, Federal University of Rio Grande do Norte, Natal, Brazil.
authors.forename: Raliny O
authors.initials: RO
authors.lastname: Santos
authors.forename: Gabriela L M
authors.initials: GL
authors.lastname: de Assunção
authors.forename: Diogo M B
authors.initials: DM
authors.lastname: de Medeiros
authors.forename: Icaro A
authors.initials: IA
authors.lastname: de Sousa Pinto
authors.forename: Keizianny S
authors.initials: KS
authors.lastname: de Barros
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Soares
authors.forename: Eunice
authors.initials: E
authors.lastname: André
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
authors.forename: Vanessa
authors.initials: V
authors.lastname: de Paula Soares-Rachetti
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy; D001362:Avoidance Learning / Q000187:drug effects; D003503:Cyclobutanes / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014151:Anti-Anxiety Agents; D003503:Cyclobutanes; C058254:sibutramine