Sulpiride, but not haloperidol, up-regulates γ-hydroxybutyrate receptors in vivo and in cultured cells

Abstract

Five days of γ-hydroxybutyrate (GHB) administration (3×500 mg kg −1 day −1 i.p.) to rats resulted in a significant decrease in the density of GHB receptors measured in the whole rat brain without modification of their corresponding affinity. Similar administration of (−)-sulpiride (2×100 mg kg −1 day −1 i.p. for 5 days) induces an up-regulation of GHB receptors without change in their dissociation constants ( K d). Haloperidol (2×2 mg day −1 i.p. for 5 days) showed no effect. Administered chronically via osmotic minipumps directly into the lateral ventricles, (−)-sulpiride (60 μg day −1 for 7 days) and GHB (600 μg day −1 for 7 days) up-regulated and down-regulated rat brain GHB receptors, respectively. Finally, in a mouse hybridoma cell line (NCB-20 cells) expressing GHB receptors, the treatment of these cells with 1 mM GHB, 100 μM (−)-sulpiride or 1 mM GABA decreases, increases and induces no change, respectively, in the density of GHB receptors 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.