Cataleptic effects of γ-hydroxybutyrate (GHB) and baclofen in mice: Mediation by GABAB receptors, but differential enhancement by N-methyl-d-aspartate (NMDA) receptor antagonists

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Rationale: Gamma-hydroxybutyrate (GHB) is a gamma-aminobutyric acid (GABA) analog that is used to treat narcolepsy but that is also abused. GHB has many actions in common with the GABAB receptor agonist baclofen, but their underlying GABAB receptor mechanisms may be different. Objective: The aim of this study is to further investigate a possible differential role of glutamate in GABAB receptor-mediated effects of GHB and baclofen. Materials and methods: The experiments examined the effects of non-competitive antagonists at the N-methyl-d-asparate (NMDA) subtype of glutamate receptors on GHB-induced catalepsy and compared these effects with those on baclofen-induced catalepsy. Results: In C57BL/6J mice, ketamine, phencyclidine (PCP), and dizocilpine (MK-801) all enhanced GHB-induced catalepsy. They did so with a potency order (i.e., MK-801 > PCP > ketamine) consistent with their relative potencies as NMDA antagonists but not as inhibitors of dopamine or organic cation transporters. Ketamine, PCP, and MK-801 enhanced catalepsy along inverted U-shaped dose-response curves likely because higher doses affected motor coordination, which limited their catalepsy-enhancing effects. Doses that were maximally effective to enhance GHB-induced catalepsy did not affect the cataleptic effects of baclofen. Conclusions: The finding that NMDA receptor antagonists enhance the cataleptic effects of GHB but not those of baclofen is further evidence that the GABAB receptor mechanisms mediating the effects of GHB and GABAB agonists are not identical. Differential interactions of glutamate with the GABAB receptor mechanisms mediating the effects of GHB and baclofen may explain why GHB is effective for treating narcolepsy and is abused, whereas baclofen is not.

Original languageEnglish (US)
Pages (from-to)191-198
Number of pages8
JournalPsychopharmacology
Volume199
Issue number2
DOIs
StatePublished - Aug 1 2008

Keywords

  • Baclofen
  • Catalepsy
  • GABA-B
  • GHB
  • Glutamate
  • Ketamine
  • MK-801
  • Mice
  • NMDA
  • PCP

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Cataleptic effects of γ-hydroxybutyrate (GHB) and baclofen in mice: Mediation by GABA<sub>B</sub> receptors, but differential enhancement by N-methyl-d-aspartate (NMDA) receptor antagonists'. Together they form a unique fingerprint.

  • Cite this