THE ANXIOLYTIC EFFECT OF GAMMA-HYDROXYBUTYRATE IN THE ELEVATED PLUS-MAZE IS REVERSED BY THE BENZODIAZEPINE RECEPTOR ANTAGONIST, FLUMAZENIL

The effects of gamma-hydroxybutyrate (GHB), a product of gamma-aminobu tyric acid (GABA) metabolism which possesses neuromodulatory propertie s in brain, were investigated in the elevated plus maze in rats. The n umber of entries and the time spent in the open arms of the maze were increased by GHB (50, 150, 250 mg/kg i.p.). This is classically consid ered as indicative of an anxiolytic effect of the drug. There was no s edative effect at these doses as measured by the spontaneous locomotor activity in the actimeter or the total number of arm entries. The anx iolytic properties of GHB were reversed by neither the GHB receptor an tagonist, NCS-382 (6,7,8,9-tetrahydro-5(H)-5-ol-ylidene acetic acid) ( 300 mg/kg i.p.), nor the opioid receptor antagonist, naloxone (10 mg/k g i.p.). However the anti-anxiety effect of GHB was antagonized by the benzodiazepine receptor antagonist, flumazenil (10 mg/kg i.p.), sugge sting an interaction of GHB with the GABA, receptor complex which medi ates the anti-anxiety effect of benzodiazepines. (C) 1998 Elsevier Sci ence B.V.