The present study was designed to evaluate the possible interaction of gamma-hydroxybutyrate (GHB) with the GABA(A) receptor complex in the rat cerebral cortex. To this purpose we studied the effect of in vitro addition and in vivo administration of GHB on the biochemical parameters currently used to evaluate the function of the GABAergic system. In vitro addition of increasing concentrations of GHB failed to modify [H-3]flunitrazepam ([H-3]FNZ) binding and the modulatory action of GABA on this binding. Moreover, unlike diazepam, GHB did not modify in vitro both muscimol-stimulated Cl-36- uptake and t-[S-35]butylbicyclophosphorothionate ([S-35]TBPS) binding to rat cerebral cortex. In vivo administration of sedative and hypnotic doses of GHB (300-750 mg/kg IP) failed to induce in 60 min any significant change in the [S-35]TBPS binding to unwashed cortical membranes. Moreover, GHB also failed to antagonize the increase in [S-35]TBPS binding (+ 55%) induced by isoniazid (350 mg/kg SC). In contrast, at the highest doses used, this drug completely antagonized the seizure activity induced by isoniazid. In conclusion, our data show that GHB fails to alter the function of the GABA(A)/benzodiazepine/ionophore receptor complex in the rat cerebral cortex.
Failure of gamma-hydroxybutyrate to alter the function of the GABAA receptor complex in the rat cerebral cortex
SERRA, MARIANGELA;SANNA E;CONCAS, ALESSANDRA;
1991-01-01
Abstract
The present study was designed to evaluate the possible interaction of gamma-hydroxybutyrate (GHB) with the GABA(A) receptor complex in the rat cerebral cortex. To this purpose we studied the effect of in vitro addition and in vivo administration of GHB on the biochemical parameters currently used to evaluate the function of the GABAergic system. In vitro addition of increasing concentrations of GHB failed to modify [H-3]flunitrazepam ([H-3]FNZ) binding and the modulatory action of GABA on this binding. Moreover, unlike diazepam, GHB did not modify in vitro both muscimol-stimulated Cl-36- uptake and t-[S-35]butylbicyclophosphorothionate ([S-35]TBPS) binding to rat cerebral cortex. In vivo administration of sedative and hypnotic doses of GHB (300-750 mg/kg IP) failed to induce in 60 min any significant change in the [S-35]TBPS binding to unwashed cortical membranes. Moreover, GHB also failed to antagonize the increase in [S-35]TBPS binding (+ 55%) induced by isoniazid (350 mg/kg SC). In contrast, at the highest doses used, this drug completely antagonized the seizure activity induced by isoniazid. In conclusion, our data show that GHB fails to alter the function of the GABA(A)/benzodiazepine/ionophore receptor complex in the rat cerebral cortex.
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