Social isolation of rats immediately after weaning is associated to a reduction in the cerebrocortical and plasma concentrations of progesterone and its metabolites 3,5-TH PROG and 3,5-THDOC. Although we found that the basal plasma concentration of adrenocorticotropic hormone in isolated rats was slightly decreased compared with that in group-housed animals no other significant changes were found in the steroidogenic machinery (peripheral benzodiazepine receptors, steroidogenic regulatory protein (StAR)). However, the functional response of the hypothalamic-pituitary-adrenal axis HPA axis to an acute stressful stimulus (foot shock), or to an acute injection of ethanol or isoniazid is markedly increased in isolated rats. Behavioral studies have also indicated that the ability of ethanol to inhibit isoniazid-induced convulsions is greater in isolated rats than in group-housed animals and this effect of isolation is prevented by treatment with the 5α-reductase inhibitor finasteride. Social isolation modified the effects of ethanol on the amounts of StAR mRNA and protein in the brain suggesting an alteration in the mechanism of cholesterol transport in mithocondria. Moreover, the amounts of the α4 and δ subunits of the GABAA receptor in the hippocampus were increased in isolated rats, and these effects were accompanied by an increase in GABAA receptor–mediated tonic inhibitory currents in granule cells of the dentate gyrus. Ethanol also increased the amplitude of GABAA receptor–mediated miniature inhibitory postsynaptic currents ( mIPSC) recorded from CA1 pyramidal neurons with a greater potency in hippocampal slices prepared from socially isolated rats than in those from group-housed, an effect inhibited by finasteride.
Social isolation stress and neuroactive steroids
SERRA, MARIANGELA;SANNA, ENRICO;
2007-01-01
Abstract
Social isolation of rats immediately after weaning is associated to a reduction in the cerebrocortical and plasma concentrations of progesterone and its metabolites 3,5-TH PROG and 3,5-THDOC. Although we found that the basal plasma concentration of adrenocorticotropic hormone in isolated rats was slightly decreased compared with that in group-housed animals no other significant changes were found in the steroidogenic machinery (peripheral benzodiazepine receptors, steroidogenic regulatory protein (StAR)). However, the functional response of the hypothalamic-pituitary-adrenal axis HPA axis to an acute stressful stimulus (foot shock), or to an acute injection of ethanol or isoniazid is markedly increased in isolated rats. Behavioral studies have also indicated that the ability of ethanol to inhibit isoniazid-induced convulsions is greater in isolated rats than in group-housed animals and this effect of isolation is prevented by treatment with the 5α-reductase inhibitor finasteride. Social isolation modified the effects of ethanol on the amounts of StAR mRNA and protein in the brain suggesting an alteration in the mechanism of cholesterol transport in mithocondria. Moreover, the amounts of the α4 and δ subunits of the GABAA receptor in the hippocampus were increased in isolated rats, and these effects were accompanied by an increase in GABAA receptor–mediated tonic inhibitory currents in granule cells of the dentate gyrus. Ethanol also increased the amplitude of GABAA receptor–mediated miniature inhibitory postsynaptic currents ( mIPSC) recorded from CA1 pyramidal neurons with a greater potency in hippocampal slices prepared from socially isolated rats than in those from group-housed, an effect inhibited by finasteride.
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