Isoniazid (375 mg/kg, s.c.), a drug that decreases GABAA receptor-mediated transmission, elicited a time-dependent increase of neuroactive steroid (pregnenolone, progesterone and allotetrahydrodeoxycorticosterone) concentrations in rat brain and plasma. This treatment also time-dependently increased the plasma concentration of corticosterone. Brain and plasma neuroactive steroid levels peaked between 40 and 120 min after isoniazid administration, respectively, and returned to control values by 5 hr. Acute foot shock stress mimicked the effect of isoniazid by increasing in a time-dependent manner the same neuroactive steroids both in brain and plasma. Abecarnil (0.3 mg/kg, i.p.), a beta-carboline derivative with anxiolytic properties, antagonized the effect of both isoniazid and foot shock on brain and plasma neuroactive steroids and on plasma corticosterone level. These data indicate that an inhibition of central GABAergic transmission enhances the concentrations of THDOC and its precursors pregnenolone and progesterone in the rat brain and plasma as well as the plasma levels of corticosterone. This finding suggests that GABA exerts a tonic inhibitory action on the mechanisms involved in the regulation of the synthesis and release of these neuroactive steroids in the central nervous system and plasma.

Barbaccia, M.l., Roscetti, G., Trabucchi, M.m., Purdy, R., Mostallino, M., Perra, C., et al. (1996). Isoniazid-induced inhibition of GABAergic transmission enhances neurosteroid content in the rat brain. NEUROPHARMACOLOGY, 35(9-10), 1299-1305.

Isoniazid-induced inhibition of GABAergic transmission enhances neurosteroid content in the rat brain

BARBACCIA, MARIA LUISA;ROSCETTI, GIANNA;TRABUCCHI, MARCO MARIO;
1996-01-01

Abstract

Isoniazid (375 mg/kg, s.c.), a drug that decreases GABAA receptor-mediated transmission, elicited a time-dependent increase of neuroactive steroid (pregnenolone, progesterone and allotetrahydrodeoxycorticosterone) concentrations in rat brain and plasma. This treatment also time-dependently increased the plasma concentration of corticosterone. Brain and plasma neuroactive steroid levels peaked between 40 and 120 min after isoniazid administration, respectively, and returned to control values by 5 hr. Acute foot shock stress mimicked the effect of isoniazid by increasing in a time-dependent manner the same neuroactive steroids both in brain and plasma. Abecarnil (0.3 mg/kg, i.p.), a beta-carboline derivative with anxiolytic properties, antagonized the effect of both isoniazid and foot shock on brain and plasma neuroactive steroids and on plasma corticosterone level. These data indicate that an inhibition of central GABAergic transmission enhances the concentrations of THDOC and its precursors pregnenolone and progesterone in the rat brain and plasma as well as the plasma levels of corticosterone. This finding suggests that GABA exerts a tonic inhibitory action on the mechanisms involved in the regulation of the synthesis and release of these neuroactive steroids in the central nervous system and plasma.
1996
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
Male; Carbolines; Progesterone; Isoniazid; Rats; Electroshock; Pregnenolone; Animals; GABA Antagonists; Anti-Anxiety Agents; Steroids; Rats, Sprague-Dawley; Brain Chemistry; Neurotransmitter Agents; Desoxycorticosterone; GABA-A Receptor Antagonists
Barbaccia, M.l., Roscetti, G., Trabucchi, M.m., Purdy, R., Mostallino, M., Perra, C., et al. (1996). Isoniazid-induced inhibition of GABAergic transmission enhances neurosteroid content in the rat brain. NEUROPHARMACOLOGY, 35(9-10), 1299-1305.
Barbaccia, Ml; Roscetti, G; Trabucchi, Mm; Purdy, R; Mostallino, M; Perra, C; Concas, A; Biggio, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/14841
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