Original Article
Neuropsychopharmacology (2005) 30, 1246–1256, advance online publication, 16 February 2005; doi:10.1038/sj.npp.1300694
Preclinical Research
Stress-Induced c-Fos Expression is Differentially Modulated by Dexamethasone, Diazepam and Imipramine
Magda Alves de Medeiros1,2, Luis Carlos Reis1 and Luiz Eugênio Mello2
- 1Department of Physiological Sciences, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil
- 2Departments of Physiology and Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil
Correspondence: Professor MA de Medeiros, Department of Physiological Sciences, Universidade Federal Rural do Rio de Janeiro, (DCF) UFRRJ, BR 464 Km 7, Seropédica, Rio de Janeiro 23890 000, Brazil. Tel: +55 21 2682 1210 R. 205; Fax: +55 21 2682 1763; E-mail: mmedeiros@ufrrj.br
Received 24 August 2004; Revised 21 December 2004; Accepted 28 December 2004; Published online 16 February 2005.
Abstract
Immobilization stress upregulates c-Fos expression in several CNS areas. Repeated stress or the use of drugs can modulate stress-induced c-Fos expression. Here, we investigated in 40 different areas of the rat brain the effects of dexamethasone (SDX, a synthetic glucocorticoid), diazepam (SBDZ, a benzodiazepine), and imipramine (IMI, an antidepressant) on the c-Fos expression induced by restraint stress. Wistar rats were divided into four groups and submitted to 20 days of daily injection of saline (three first groups) or imipramine, 15 mg/kg, i.p. On day 21, animals were submitted to injections of saline (somatosensory, SS), SDX (1 mg/kg, i.p.), SBDZ (5 mg/kg, i.p.), or IMI (15 mg/kg, i.p.) before being submitted to restraint. Immediately after stress, the animals were perfused and their brains processed with immunohistochemistry for c-Fos (Ab-5 Oncogene Science). Dexamethasone reduced stress-induced c-Fos expression in SS cortex, hippocampus, paraventricular nucleus of the hypothalamus (PVH), and locus coeruleus (LC), whereas diazepam reduced c-Fos staining in the SS cortex, hippocampus, bed nucleus of stria terminalis, septal area, and hypothalamus (preoptic area and supramammillary nucleus). Chronic administration of imipramine decreased staining in the hippocampus, PVH, and LC, while increasing it in the nucleus raphe pallidus. We conclude that dexamethasone, diazepam and imipramine differentially modulate stress-induced Fos expression. The present study provides an important comparative background that may help in the further understanding of the effects of these compounds and on the brain activation as well as on the behavioral, neuroendocrine, and autonomic responses to stress.
Keywords:
immediate-early genes, c-Fos, restraint stress, antidepressants, glucocorticoids, benzodiazepines
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