Gamma-OH and Flumazenil

patanie at pasdepub.com patanie at pasdepub.com
Wed Aug 12 11:52:57 EST 1998


Eur J Pharmacol 1998 Jan 19;342(1):21-27 

The anxiolytic effect of gamma-hydroxybutyrate in the
elevated plus maze is reversed by the benzodiazepine
receptor antagonist, flumazenil.

Schmidt-Mutter C, Pain L, Sandner G, Gobaille S, Maitre M

Centre de Neurochimie, UPR 416 CNRS, and Departement
d'Anesthesie-Reanimation, Hopitaux
Universitaires de Strasbourg, France. mutter at neurochem.u-strasbg.fr 

The effects of gamma-hydroxybutyrate (GHB), a product of
gamma-aminobutyric acid (GABA)
metabolism which possesses neuromodulatory properties in brain, were
investigated in the elevated
plus maze in rats. The number 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
considered as indicative of an
anxiolytic effect of the drug. There was no sedative effect at these
doses as measured by the
spontaneous locomotor activity in the actimeter or the total number of
arm entries. The anxiolytic
properties of GHB were reversed by neither the GHB receptor
antagonist, NCS-382
(6,7,8,9-tetrahydro-5(H)-5-olylidene acetic acid) (300 mg/kg i.p.),
nor the opioid receptor
antagonist, naloxone (10 mg/kg i.p.). However the anti-anxiety effect
of GHB was antagonized by
the benzodiazepine receptor antagonist, flumazenil (10 mg/kg i.p.),
suggesting an interaction of GHB
with the GABA(A) receptor complex which mediates the anti-anxiety
effect of benzodiazepines. 

PMID: 9544788, UI: 98204348 


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