Effects of chronic treatment with corticosterone and imipramine on fos immunoreactivity and adult hippocampal neurogenesis

In a previous study we showed that rats chronically treated with corticosterone (CORT) display anxiogenic behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. Treatment with the tricyclic antidepressant imipramine significantly reversed the anxiogenic effects of CURT, while inhibiting ETM escape, a response related to panic disorder. To better understand the neurobiological mechanisms underlying these behavioral effects, analysis of c-fos protein immunoreactivity (fos-ir) was used here to map areas activated by chronic CORT (200 mg pellets, 21-day release) and imipramine (15 mg/kg, IP) administration. We also evaluated the number of cells expressing the neurogenesis marker doublecortin (DCX) in the hippocampus and measured plasma CURT levels on the 21st day of treatment. Results showed that CURT increased fos-ir in the ventrolateral septum, medial amygdala and paraventricular hypothalamic nucleus and decreased fos-ir in the lateral periaqueductal gray. Imipramine, on the other hand, increased fos-ir in the medial amygdala and decreased fos-ir in the anterior hypothalamus. CURT also decreased the number of DCX-positive cells in the ventral and dorsal hippocampus, an effect antagonized by imipramine. CURT levels were significantly higher after treatment. These data suggest that the behavioral effects of CURT and imipramine are mediated through specific, at times overlapping, neuronal circuits, which might be of relevance to a better understanding of the physiopathology of generalized anxiety and panic disorder. (c) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, UNIFESP, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Biosci, Santos, BrazilUniv São Paulo, Dept Physiol & Biophys, Inst Biomed Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Acad Off, UNIFESP, Santos, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Biosci, Santos, BrazilUniversidade Federal de São Paulo, Acad Off, UNIFESP, Santos, SP, BrazilFAPESP: 2008/58815-1FAPESP: 2009/50830-4Web of Scienc