Unravelling the brain targets of γ-hydroxybutyric acid

Vincenzo Crunelli, Z. Emri, Nathalie Leresche

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

γ-Hydroxybutyric acid (GHB) is a naturally occurring γ-aminobutyric acid (GABA) metabolite that has been proposed as a neurotransmitter/neuromodulator that acts via its own receptor (GHBR). Its exogenous administration, however, elicits central nervous system-dependent effects (e.g. memory impairment, increase in sleep stages 3 and 4, dependence, seizures and coma) that are mostly mediated by GABAB receptors. The past few years have seen important developments in our understanding of GHB neurobiology: A putative GHBR has been cloned; a transgenic model of GHB aciduria has been developed; GABAB receptor knockout mice and novel GHB analogs have helped to characterize the vast majority of exogenous GHB actions mediated by GABAB receptors; and some of the cellular mechanisms underlying the dependence/abuse properties of GHB, and its ability to elicit absence seizures and an increase in sleep stages 3 and 4, have been clarified. Nevertheless, the physiological significance of a brain GHB signaling pathway is still unknown, and there is an urgent need for a well-validated functional assay for GHBRs. Moreover, as GHB can also be metabolized to GABA, it remains to be seen whether the many GABAB receptor-mediated actions of GHB are caused by GHB itself acting directly on GABAB receptors or by a GHB-derived GABA pool (or both).

Original languageEnglish
Pages (from-to)44-52
Number of pages9
JournalCurrent Opinion in Pharmacology
Volume6
Issue number1 SPEC. ISS.
DOIs
Publication statusPublished - Feb 2006

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Hydroxybutyrates
gamma-Aminobutyric Acid
Sleep Stages
Neurotransmitter Agents
Brain
Aminobutyrates
Absence Epilepsy
Aptitude
Neurobiology
Coma
Knockout Mice
Seizures
Central Nervous System

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Unravelling the brain targets of γ-hydroxybutyric acid. / Crunelli, Vincenzo; Emri, Z.; Leresche, Nathalie.

In: Current Opinion in Pharmacology, Vol. 6, No. 1 SPEC. ISS., 02.2006, p. 44-52.

Research output: Contribution to journalArticle

Crunelli, Vincenzo ; Emri, Z. ; Leresche, Nathalie. / Unravelling the brain targets of γ-hydroxybutyric acid. In: Current Opinion in Pharmacology. 2006 ; Vol. 6, No. 1 SPEC. ISS. pp. 44-52.
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