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

Eur J Pharmacol. 1998 Apr 10;346(2-3):331-7. doi: 10.1016/s0014-2999(98)00068-5.


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 density of GHB receptors measured in the whole rat brain without modification of their corresponding affinity. Similar administration of (-)-sulpiride (2 X 100 mg kg(-1) day(-1) i.p. for 5 days) induces an up-regulation of GHB receptors without change in their dissociation constants (Kd). Haloperidol (2 X 2 mg day(-1) i.p. for 5 days) showed no effect. Administered chronically via osmotic minipumps directly into the lateral ventricles, (-)-sulpiride (60 microg day(-1) for 7 days) and GHB (600 microg 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 microM (-)-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Chemistry / drug effects
  • Cell Line
  • Cells, Cultured
  • Dopamine Antagonists / pharmacology*
  • Haloperidol / pharmacology*
  • Injections, Intraventricular
  • Kinetics
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / drug effects*
  • Sodium Oxybate / pharmacology
  • Sulpiride / pharmacology*
  • Up-Regulation / drug effects*


  • 4-hydroxybutyric acid receptor
  • Dopamine Antagonists
  • Receptors, Cell Surface
  • Sodium Oxybate
  • Sulpiride
  • Haloperidol