Psychopharmacology

, Volume 192, Issue 3, pp 407–414

Cataleptic effects of γ-hydroxybutyrate (GHB), its precursor γ-butyrolactone (GBL), and GABAB receptor agonists in mice: differential antagonism by the GABAB receptor antagonist CGP35348

Original Investigation

Abstract

Rationale

Gamma-hydroxybutyrate (GHB) is used to treat narcolepsy but is also abused. GHB has many actions in common with the GABAB receptor agonist baclofen.

Objective

To further study the role of GABAB receptors in the effects of GHB.

Materials and methods

The experiments examined the ability of the GABAB receptor antagonist CGP35348 to attenuate GHB-induced catalepsy in comparison with its ability to attenuate the cataleptic effects of GABAB receptor agonists.

Results

In C57BL/6J mice, GHB, the GHB precursor gamma-butyrolactone (GBL), and the GABAB receptor agonists baclofen and SKF97541 all produced catalepsy but differed in potency (i.e., SKF97541>baclofen>GBL>GHB) and in onset of action. The cataleptic effects of drug combinations were assessed at the time of peak effect of each compound, i.e., 60 min after CGP35348 and 60, 30, 30, and 15 min after baclofen, SKF97541, GHB, and GBL, respectively. At 100 mg/kg, CGP35348 shifted the dose–response curves of baclofen and SKF97541 to the right but not those of GHB and GBL; at 320 mg/kg, CGP35348 shifted the curves of all four compounds to the right.

Conclusions

The finding that CGP35348 was about threefold less potent to antagonize GHB and GBL than baclofen and SKF97541 is further evidence that the mechanisms mediating the effects of GHB and GABAB agonists are not identical. Differential involvement of GABAB receptor subtypes, or differential interactions with GABAB receptors, may possibly explain why GHB is effective for treating narcolepsy and is abused whereas baclofen is not.

Keywords

Catalepsy Mice GHB GBL Baclofen SKF97541 CGP35348 GABA GABA-B 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of PsychiatryThe University of Texas Health Science Center at San AntonioSan AntonioUSA
  2. 2.Department of PharmacologyThe University of Texas Health Science Center at San AntonioSan AntonioUSA
  3. 3.Department of Pharmaceutical SciencesUniversity of MarylandBaltimoreUSA

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