title: The differential effects of chronic imipramine or citalopram administration on physiological and behavioral outcomes in naïve mice.
abstract: Tricyclics and selective serotonin reuptake inhibitors (SSRIs) are probably the most widely employed reference antidepressants in animal studies on depression. Using imipramine and citalopram, we sought to assess which drug would be more appropriate as pharmacological reference in paradigms of depression in C57BL6N mice by measuring their effect on liquid consumption, home cage activity, body weight and long-term memory in naïve animals treated with each compound at generally used dose of 15 mg/kg/day. Continuous logging of home cage movement, weekly monitoring of vertical activity in a novel cage, and body weight was recorded during four-week treatment period and for four weeks after discontinuation of the antidepressant; sucrose preference was evaluated at weekly intervals during drug administration. A novel object recognition memory test was performed in mice treated the antidepressants for two weeks. Compared to control, imipramine-treated mice displayed increased sucrose and water intake, as well as enhanced home-cage and novelty exploration activities, and reduced body weight. Imipramine also impaired learning in the object recognition task, but citalopram diminished object exploration sufficiently to invalidate the test. Citalopram-treated animals demonstrated no changes in a sucrose test and had elevated body mass. Thus basic physiological and behavioral outcomes in naïve mice were significantly altered by the chronic administration of imipramine and, to a lesser extent, citalopram. As altered variables are crucial for the evaluation of antidepressant-like effects in mice, our data suggest that, at commonly used doses, both drugs must be applied in mouse models of depression with caution.
authors: Maastricht Medical Center in Annadal, Department of Preventive Medicine, Becanusstraat 17 A0, 6216 BX Maastricht, The Netherlands. t.strekalova@maastrichtuniversity.nl
authors: Tatyana
authors: T
authors: Strekalova
authors: Daniel C
authors: DC
authors: Anthony
authors: Oleg
authors: O
authors: Dolgov
authors: Konstantin
authors: K
authors: Anokhin
authors: Aslan
authors: A
authors: Kubatiev
authors: Harry M W
authors: HM
authors: Steinbusch
authors: Careen
authors: C
authors: Schroeter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D004326:Drinking; D016503:Drug Delivery Systems; D005106:Exploratory Behavior / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013395:Sucrose
chemical_list: D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors; D013395:Sucrose