Blockade of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB) by the GHB receptor antagonist NCS-382.

The present study was designed to assess the ability of the newly synthetized, selective gamma-hydroxybutyric acid (GHB) receptor antagonist, NCS-382, in blocking the discriminative stimulus effects of GHB in a T-maze, food-reinforced drug discrimination procedure. Two groups of rats were trained to run the left arm of the maze 30 min after the i.g. administration of either 300 or 700 mg/kg GHB and the right arm after water. Once discrimination was acquired, combination of different doses of NCS-382 (0, 12.5, 25.0 and 50.0 mg/kg, IP) and GHB training doses were tested for blockade of GHB discrimination. NCS-382 dose-dependently blocked GHB-appropriate responding in both the 300 and 700 mg/kg GHB rat groups. The results of the present study indicate that the discriminative stimulus properties of GHB are mediated via stimulation of GHB receptors.