Effect of corticosteroids on neurotransmitter metabolism in rat central nervous system

Abstract

Present data indicates that hormones especially corticosteroids, apart from being responsible for functional changes in the CNS, also bring about changes which alter the general metabolism of the brain, thus affecting different aspecLs of the neurotransmitter, plastic and energetic functions of the neurone. It is generally accepted that one of the most plastic morphofunctional structures of the CNS is the synapse, and most neurotropic compounds including steroid hormones affect neuronal activity and other associated structures by affecting synaptic transmission. Hormones can alter the levels of neurotransmitters in certain regions of the central and peripheral nervous system by either altering their data of synthesis or degradation, i.e. by affecting the activities of the enzymes responsible for their metabolism. The study has examined the metabolism of several biogenic amines GABA, Nlrepinephrine (NE) Dopamine (OA) and Serotonin (S-Hl) and how their metabolism is affected by different corticosteroid leve~. In an attempt to elucidate the biochemical basis of behavioural effects of corticosteroids, we have studied t he influence of two of these hc r-mo ne s . hy dr-o co rt isone and dexamethasone on the relative concentrations of NE, OA, 5-HT and GABA and their metabolic enzymes in discrete regions of the brain with special emphasis being paid to the limbic structures especially the hypothalamus and hippocampus. We used a model of single and mUltiple administration of high doses of the hormones which causes hyper and hypocortisolism in blood plasma respectively. We have also studied how the metabolic enzymes vary under these hormonal conditions. The results of our study show that alteration of corticosteroid status of rats, does cause changes in the concentrations of the putative neurotransmitters sufficient to cause gross behavioral changes. The data also indicates that changes seen in brain NE, OA, 5-HT and GABA are modulated through adrenocortical steroids and that these hormones playa role in the regulation of biogenic amine metabolism. It is suggested that corticosteroids could be used in therapy of affective disorders. The work is original and helps to expand and shed more light on available data on the control of neurolransmitter metabolism by steroid hormones and possible control mechanisms.