Portal de Periódicos da CAPES

Role of GABAB receptors in the sedative/hypnotic effect of γ-hydroxybutyric acid

2001; Elsevier BV; Volume: 428; Issue: 3 Linguagem: Inglês

10.1016/s0014-2999(01)01334-6

1879-0712

Mauro A.M. Carai, Giancarlo Colombo, Giuliana Brunetti, Samuele Melis, Salvatore Serra, Giovanni Vacca, Sarah Mastinu, A.M. Pistuddi, C. Solinas, Giorgio Cignarella, G Minardi, G L Gessa,

Neurotransmitter Receptor Influence on Behavior

The present study was aimed at identifying the receptor systems involved in the mediation of the sedative/hypnotic effect of γ-hydroxybutyric acid (GHB) in DBA mice. Administration of the putative antagonist of the GHB binding site, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382; 50–500 mg/kg, i.p.), significantly increased the duration of loss of righting reflex induced by GHB (1000 mg/kg, i.p.). In contrast, the GABAB receptor antagonists, (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 25–100 mg/kg, i.p.) and (3-aminopropyl)(cyclohexylmethyl)phosphinic acid (CGP 46381; 12.5–150 mg/kg, i.p.), completely prevented the sedative/hypnotic effect of GHB. SCH 50911 (100 and 300 mg/kg, i.p.) was also capable to readily reverse the sedative/hypnotic effect of GHB (1000 mg/kg, i.p.) in mice that had lost the righting reflex. SCH 50911 (100 mg/kg, i.p.) also completely abolished the sedative/hypnotic effect of the GABAB receptor agonist, baclofen. These results indicate that the sedative/hypnotic effect of GHB is mediated by the stimulation of GABAB receptors and add further support to the hypothesis that the GABAB receptor constitutes a central site of action of GHB.