Corticosterone Treatment Of Rats Research Articles

Attenuated disruption of prepulse inhibition by dopaminergic stimulation after maternal deprivation and adolescent corticosterone treatment in rats

The development of schizophrenia may include an early neurodevelopmental stress component which increases vulnerability to later stressful life events, in combination leading to overt disease. We investigated the effect of an early stress, in the form of maternal deprivation, combined with a later stress, simulated by chronic periadolescent corticosterone treatment, on behaviour in rats. Acute treatment with apomorphine caused disruption of prepulse inhibition (PPI) in controls and in rats that had undergone either maternal deprivation or corticosterone treatment, but was surprisingly absent in rats that had undergone the combined early and late stress. Amphetamine treatment significantly disrupted PPI in both non-deprived groups, but was absent in both maternally deprived groups. The serotonin-1A receptor agonist, 8-OH-DPAT, induced a significant disruption of PPI in all groups. Amphetamine-induced locomotor hyperactivity was similar in all groups. These results show an inhibitory interaction of early stress, caused by maternal deprivation, combined with ‘adolescent’ stress, simulated by corticosterone treatment, on dopaminergic regulation of PPI. The altered effects of apomorphine and amphetamine could indicate differential changes in dopamine receptor signalling leading to functional desensitisation, or altered modulation of sensory gating in the nucleus accumbens by limbic structures such as the hippocampus.

Early postnatal corticosterone administration regulates neurotrophins and their receptors in septum and hippocampus of the rat.

The principal glucocorticoid in rats, corticosterone, interacts with neurons in the limbic system and leads to morphological and behavioral changes. Putative corticosterone-triggered mediators are neurotrophins. In the present study we investigated the effects of early postnatal corticosterone treatment in rats on neurotrophic factors of the nerve growth factor (NGF) family and their receptors. Newborn rats were treated with corticosterone-containing polymers until postnatal day 12. The mRNA and protein levels of the neurotrophins of the NGF family (NGF, BDNF, NT-3 and NT-4/5) and their receptors (trkA, trkB, trkC and p75) were quantified in septum and hippocampus using RT-PCR. In the septal region, we found an unchanged mRNA expression after corticosterone treatment, whereas in the hippocampus there was a general increase in mRNA. Particularly, the gene expression of NGF, NT-3, and the high affinity receptors trkA, trkB and trkC increased significantly. Quantification of the neurotrophin protein levels using an ELISA revealed significant treatment effects for NGF and NT-4/5 in the hippocampus. The present study of corticosterone treatment in young rats demonstrates interactions of steroid hormones with neurotrophic factors and their receptors in the septo-hippocampal system during the first two postnatal weeks.

Bcl-2 and Bax expression in cartilage and bone cells after high-dose corticosterone treatment in rats

The expression of Bcl-2 and Bax has been evaluated by immunohistochemistry in normal rats, and in rats after treatment with high-dose corticosterone (CORT). Proliferative (PC) and maturative/hypertrophic (MaHC) chondrocytes of the growth plate have been examined, as well as osteoblasts (Obs), osteocytes (Ots) and osteoclasts (Ocs) of the metaphyseal secondary spongiosa. For each cell type, the Bcl-2 and Bax immunopositive cells were expressed as a percentage of the total number of cells. Bcl-2 and Bax expression was considered to be enhanced when the percentage of positive cells rose. Bcl-2 and Bax were expressed in all cell types, and two main kinds of labeling distribution, both suggestive of association with intracellular organelles, were observed in the cytoplasm: scarce and spotty labeling (type 1) or abundant, granular and diffuse labeling (type 2). In some cases, nuclear membranes could also be seen to be positive. Positive PCs and Obs generally showed a labeling of type 1, MaHCs and Ocs of type 2, while Ots varied with labeling of type 1 or type 2. CORT administration induced a fall in the percentage of Bcl-2 immunopositive cells, and a rise in that of Bax immunopositive cells, in PCs and Ots. The same trend was observed in MaHCs, although the Bcl-2 decrease was not significant. The percentage of Bcl-2 and Bax immunopositive Obs rose, and their labeling distribution shifted from type 1- to type 2-labeled cells. Ocs showed the highest immunopositivity for both Bcl-2 and Bax, which did not change after CORT administration. These data suggest that CORT treatment, by lowering Bcl-2, and raising Bax expression, may promote the apoptotic process in PCs, MaHCs and Ots. Obs, however, do not undergo the same variations. This finding, together with the results of a previous study showing that CORT administration raises the frequency of apoptotic Obs, does not support a direct relationship between apoptosis and Bax overexpression, at least in Obs. The CORT effect might be related to cell types and their state of differentiation, so that Bcl-2 and Bax might regulate not only the machinery of cell death, but also cell proliferation and differentiation.

Effects of corticosterone on phosphorylation of rat liver nuclear proteins in vitro.

SummaryGlucocorticoids are known to bind to liver cytosol proteins and alter nuclear RNA synthesis. Nuclear proteins are believed to assist in the regulation of nuclear RNA synthesis. The work reported here tested the possibilities that one of the very early effects of corticosterone treatment in rats consists of altered phosphorylation of nuclear proteins and that cytosol steroid-receptor complexes are necessary for altered phosphorylation of nuclear proteins.It was found that phosphorylation of proteins in liver nuclei isolated from rats previously injected with corticosterone was significantly (p < 0.05) greater than control. Corticosterone in vitro had no effect when incubated directly with nuclei, but phosphorylation was significantly (p < 0.05) increased in nuclei previously incubated with rat liver cytosol containing 10−7M corticosterone.Corticosterone treatment increased phosphorylation in histones and nuclear acidic proteins. Although phosphorylation of histones was generally increased, no select...