1. ¹Center for Neurobiology and Behavior, Columbia University, New York, NY, USA
2. ²Department of Pharmacology, Columbia University, New York, NY, USA
3. ³Department of Psychiatry, Columbia University, New York, NY, USA

Correspondence: R Hen, Center for Neurobiology and Behavior, Columbia University, PI Annex, Room 725, 722 West 168th St, New York, NY 10032, USA. Tel: +1 212 543 5137; Fax: +1 212 543 5074; E-mail: rh95@columbia.edu

Received 6 October 2003; Revised 29 January 2004; Accepted 5 February 2004; Published online 7 April 2004.

Abstract

The onset of the therapeutic response to antidepressant treatment exhibits a characteristic delay. Animal models sensitive to chronic, but not acute, antidepressant treatment are greatly needed for studying antidepressant mechanisms. We initially assessed four inbred mouse strains for their behavioral response to chronic treatment with the selective-serotonin reuptake inhibitor fluoxetine (0, 5, 10 mg/kg/day in drinking water), which is used for the treatment of mood and anxiety disorders. Only the highly anxious BALB/c strain exhibited sensitivity to fluoxetine in the forced swim test. Additionally, fluoxetine reduced locomotion in C57BL/6 and 129SvEv, but not BALB/c and DBA/2, strains. We then evaluated the effects of subchronic (4 days) and chronic (24 days) fluoxetine treatment (0, 10, 18, 25 mg/kg/day) on measures of anxiety and depression in BALB/c mice. Anxiety measures were obtained using the open field and novelty-induced hypophagia tests. Antidepressant effects were evaluated using the forced swim test. We found 18 mg/kg/day of chronic fluoxetine to be active in all three paradigms; subchronic treatment had no effect. Anxiety-related measures were reduced by 18 mg/kg/day. In the forced swim test, 10 and 18 mg/kg/day increased swimming and reduced immobility. Here we present several novel effects of chronic, but not subchronic, antidepressant treatment.