SULPIRIDE, BUT NOT HALOPERIDOL, UP-REGULATES GAMMA-HYDROXYBUTYRATE RECEPTORS IN-VIVO AND IN CULTURED-CELLS

Five days of gamma-hydroxybutyrate (GHB) administration (3 x 500 mg kg (-1) day(-1) i.p.) to rats resulted in a significant decrease in the d ensity of GHB receptors measured in the whole rat brain without modifi cation of their corresponding affinity. Similar administration of (-)- sulpiride (2 x 100 mg kg(-1) day(-1) i.p. for 5 days) induces an up-re gulation of GHB receptors without change in their dissociation constan ts (K-d). Haloperidol (2 x 2 mg day(-1) i.p. for 5 days) showed no eff ect. Administered chronically via osmotic minipumps directly into the lateral ventricles, (-)-sulpiride (60 mu g day(-1) for 7 days) and GHB (600 mu g day(-1) for 7 days) up-regulated and down-regulated rat bra in GHB receptors, respectively. Finally, in a mouse hybridoma cell lin e (NCB-20 cells) expressing GHB receptors, the treatment of these cell s with 1 mM GHB, 100 mu M (-)-sulpiride or 1 mM GABA decreases, increa ses and induces no change, respectively, in the density of GHB recepto rs after 3 days of treatments. These results indicate that chronic GHB treatment modifies the expression of its receptor and that sulpiride also induces plastic changes in GHB receptors perhaps via antagonistic properties. (C) 1998 Elsevier Science B.V.