Abstract
The aim of this study was to examine the effects of single-dose and chronic corticosterone treatment on the inducible transcription factor c-Fos and FosB, and thereby to estimate the effects of high-doses of corticosterone on calcium-dependent neuronal responses in the rat cerebral cortex. At the same time we investigated the distribution of interneurons containing calretinin (CR), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in chronically treated animals in order to collect data on the involvement of inhibitory neurons in this process. Adult male rats were injected subcutaneously with 10mg corticosterone, whereas controls received the vehicle (sesame oil). The animals were fixed by transcardial perfusion 12 and 24h following single corticosterone injection, and the brains were processed for c-Fos and FosB immunohistochemistry. To investigate the effects of repeated corticosterone administration, rats were daily treated with the same amount of corticosterone (10mg/animal, subcutaneously) for 21 days. Controls were injected with vehicle. At the end of the experiment, the rats were perfused and immunohistochemistry was used to detect the presence of the FosB protein, CR, VIP and NPY. Quantitative evaluation of immunolabelled cells was performed in the neocortex and the hippocampus. The number of immunoreactive nuclei per unit area was used as a quantitative measure of the effects of corticosterone. It was found that a single-dose administration of corticosterone resulted in a significant, time-dependent increase of c-Fos protein immunoreactivity in the granule cell layer of the dentate gyrus, as well as in regions CA1 and CA3 of the hippocampus 12 and 24h post-injection with respect to control animals. Significant enhancement of c-Fos immunoreactivity was also observed in the neocortex at 12 and 24h post-injection. Single-dose treatment did not significantly alter FosB immunolabelling. Repeated administration of corticosterone produced a complex pattern of changes in FosB immunolabelling: significant increase in FosB immunoreactivity was detected in the granule cell layer of the dentate gyrus, with no significant changes in the CA1 and CA3 layers of the hippocampus and in the neocortex. However, a significant decrease of FosB induction in the neocortex was observed in chronically treated rats in comparison to single-dose injected animals (12h before immunohistochemistry). Analysis of immunohistochemical detection of interneuronal markers revealed a significant reduction of the CR immunolabelling in the CA3 area of the hippocampus. No changes in VIP or NPY immunoreactivity were found in the Ammon's horn 3 weeks following daily corticosterone treatment. NPY immunoreactivity was significantly attenuated in the neocortex. The present data suggest that single-dose corticosterone treatment increases immunoreactivity of c-Fos protein in a time-dependent manner, 12 and 24h post-injection in the rat hippocampus and the neocortex, whereas chronic corticosterone treatment influences FosB immunoreactivity, primarily in the dentate gyrus. Chronic corticosterone administration seems to affect CR levels in the CA3 area of the hippocampus.
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