Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in rats

The aim of the present study was to investigate the anxiolytic effects of l ong-term treatment with fluoxetine in rats. Selective serotonin reuptake in hibitors (SSRIs), such as fluoxetine, are used to treat anxiety and panic d isorders, in addition to treating depression. A major concern with SSRIs is a 2-3-week delay in their therapeutic effects. SSRIs share with anxiolytic 5-HT1A agonists the ability to produce desensitization of post-synaptic 5- HT1A receptors. To investigate the anxiolytic effects of fluoxetine, rats w ere treated for 14 days with fluoxetine (10 mg kg(-1) day(-1), i.p.). The r ats were stressed using a conditioned stress procedure and tested one day a fter the last fluoxetine injection. Fluoxetine decreased stress-induced def ecation (by 60%), reversed the stress-induced suppression of exploring beha vior (by 59%) and shortened the duration of stress-induced freezing behavio r (by 11.5%). However, the stress-induced increase in plasma levels of ACTH , corticosterone, oxytocin, prolactin and renin were not inhibited by fluox etine treatment. These findings suggest that neuroadaptive changes induced by sustained inhibition of serotonin (5-HT) reuptake, contribute to the mec hanism of the anxiolytic effects of fluoxetine. in contrast, the neuroendoc rine responses to conditioned stress are not affected by these neuroadaptiv e changes. (C) 2000 Elsevier Science B.V. All rights reserved.