Stress-induced c-Fos expression is differentially modulated by dexamethasone, diazepam and imipramine

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.UFRRJ, Dept Physiol Sci, BR-23890000 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilWeb of Scienc

Corticosteroids : sculptors of the hippocampal formation

The influence of corticosteroids on hippo-campus-dependent learning and memory processes is now indisputable. On the other hand, closer scrutiny of early studies together with interpretations from newer studies would suggest that the proposition that corticosteroid-induced hippocampal cell death accounts fully for the associated cognitive deficits is only partially correct. Firstly, it is now clear that a specific sub-population of hippocampal neurons, the granule cells of the dentate gyrus, is more sensitive to changes in the cortiscosteroid environment; this fact raises the interesting question of what might be the unique properties of granule cells that render them more vulnerable to these hormones, since virtually all hippocampal cells express corticosteroid receptors. Secondly, from a critical analysis of the available data, the picture that emerges is that costicosteroids, by acting through two distinct receptors, influence not only cell birth and death, but probably also cell differentiation. Mineralocorticoid receptor (MR) occupation appears to be essential for the survival of existing and newly generated granule neurons. In contrast, while glucocorticoid receptors (GR)can induce loss of neurons in the absence of MR activation, it appears that their occupation usually results in less drastic effects involving only dentritic atrophy and loss of synaptic contacts. This revised scheme of corticosteroid actions on hippocampal structure should explain earlier observations that many of the cognition-impairing effects of the corticosteroids are reversible.Institute of Anatomy of Porto Medical School. Max Planck Society. Acções Integradas Luso-Alemãs