title: Effects of chronic treatment with corticosterone and imipramine on fos immunoreactivity and adult hippocampal neurogenesis.
abstract: 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 CORT, 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 CORT levels on the 21st day of treatment. Results showed that CORT 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. CORT also decreased the number of DCX-positive cells in the ventral and dorsal hippocampus, an effect antagonized by imipramine. CORT levels were significantly higher after treatment. These data suggest that the behavioral effects of CORT 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.
authors.affiliation: Department of Psychiatry, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Diniz
authors.forename: T B
authors.initials: TB
authors.lastname: dos Santos
authors.forename: L R G
authors.initials: LR
authors.lastname: Britto
authors.forename: I C
authors.initials: IC
authors.lastname: Céspedes
authors.forename: M C
authors.initials: MC
authors.lastname: Garcia
authors.forename: R C
authors.initials: RC
authors.lastname: Spadari-Bratfisch
authors.forename: C C
authors.initials: CC
authors.lastname: Medalha
authors.forename: G M
authors.initials: GM
authors.lastname: de Castro
authors.forename: F T
authors.initials: FT
authors.lastname: Montesano
authors.forename: M B
authors.initials: MB
authors.lastname: Viana
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D007099:Imipramine; D003345:Corticosterone