The progesterone derivative 3 alpha-hydroxy-5 alpha-pregnan-20 one (allopregnanolone/AP) and the deoxycorticosterone derivative 3 alpha-21-dihydroxy-5 alpha-pregnan-20 one (allotetrahydrodeoxycorticosterone/THDOC) are endogenous neuroactive steroids endowed with neuromodulatory actions in the central nervous system. Their best-characterized membrane-receptor-dependent action consists in the amplification of GABA-gated chloride currents mediated by specific interactions with the GABA, receptor complex, which appears responsible for the pharmacological effects (anxiolytic, anticonvulsant, hypnotic/anaesthetic) of exogenously administered AP and THDOC. Several acute stress paradigms and different negative allosteric modulators (isoniazid and FG 7142) of GABA(A) receptors time dependently increase brain and plasma concentrations of AP and THDOC only in intact or sham-operated but not in adrenalectomized-orchiectomized rats. These results suggest that acute stress and inhibitors of GABA(A) receptors increase the brain and plasma neurosteroid concentrations via a reduction of the inhibitory action exerted by GABA on the hypothalamic-pituitary-adrenal axis. The comparison between the time course of the changes in GABA(A) receptor function and of their behavioral correlates (proconflict behavior) and that of the changes of endogenous neuroactive steroids are consistent with the view that AP and THDOC may play a role in restoring the GABAergic tone to prestress conditions, by limiting the duration and the extent of its stress-induced reduction. The acute stress-elicited increase of AP and THDOC is observed in adult as well as in aged rats, which show a reduced basal GABAergic transmission and a greater response to the effect of stress in terms of their brain cortical neuroactive steroid concentrations than adult rats. (C) 1998 Elsevier Science Inc.

Barbaccia, M.l., Concas, A., Serra, M., & Biggio, G. (1998). Stress and neurosteroids in adult and aged rats. In Experimental Gerontology (pp.697-712). OXFORD : PERGAMON-ELSEVIER SCIENCE LTD [10.1016/S0531-5565(98)00042-4].

Stress and neurosteroids in adult and aged rats

BARBACCIA, MARIA LUISA;
1998

Abstract

The progesterone derivative 3 alpha-hydroxy-5 alpha-pregnan-20 one (allopregnanolone/AP) and the deoxycorticosterone derivative 3 alpha-21-dihydroxy-5 alpha-pregnan-20 one (allotetrahydrodeoxycorticosterone/THDOC) are endogenous neuroactive steroids endowed with neuromodulatory actions in the central nervous system. Their best-characterized membrane-receptor-dependent action consists in the amplification of GABA-gated chloride currents mediated by specific interactions with the GABA, receptor complex, which appears responsible for the pharmacological effects (anxiolytic, anticonvulsant, hypnotic/anaesthetic) of exogenously administered AP and THDOC. Several acute stress paradigms and different negative allosteric modulators (isoniazid and FG 7142) of GABA(A) receptors time dependently increase brain and plasma concentrations of AP and THDOC only in intact or sham-operated but not in adrenalectomized-orchiectomized rats. These results suggest that acute stress and inhibitors of GABA(A) receptors increase the brain and plasma neurosteroid concentrations via a reduction of the inhibitory action exerted by GABA on the hypothalamic-pituitary-adrenal axis. The comparison between the time course of the changes in GABA(A) receptor function and of their behavioral correlates (proconflict behavior) and that of the changes of endogenous neuroactive steroids are consistent with the view that AP and THDOC may play a role in restoring the GABAergic tone to prestress conditions, by limiting the duration and the extent of its stress-induced reduction. The acute stress-elicited increase of AP and THDOC is observed in adult as well as in aged rats, which show a reduced basal GABAergic transmission and a greater response to the effect of stress in terms of their brain cortical neuroactive steroid concentrations than adult rats. (C) 1998 Elsevier Science Inc.
4th International Symposium on the Neurobiology and Neuroendocrinology of Aging
BREGENZ, AUSTRIA
JUL 26-31, 1998
SO Ill Univ, Sch Med, RW Johnson Pharmaceut Res Inst, Junifur Fdn, Orentreich Fdn Advancement Sci, Searle Pharmaceut, SO Ill Univ, Grad Sch
Rilevanza internazionale
Settore BIO/14
English
foot-shock stress; CO2 inhalation; neurosteroids; GABA(A) receptor; HPA axis; rats
Intervento a convegno
Barbaccia, M.l., Concas, A., Serra, M., & Biggio, G. (1998). Stress and neurosteroids in adult and aged rats. In Experimental Gerontology (pp.697-712). OXFORD : PERGAMON-ELSEVIER SCIENCE LTD [10.1016/S0531-5565(98)00042-4].
Barbaccia, Ml; Concas, A; Serra, M; Biggio, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/49673
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