Gamma-hydroxybutyric acid decreases intravenous cocaine self- administration in rats

M. Cristina Martellotta, Claudia Balducci, Liana Fattore, Gregorio Cossu, Gian Luigi Gessa, Luigi Pulvirenti, Walter Fratta

Research output: Contribution to journalArticle


Gamma-hydroxybutyric acid (GHB) is an endogenous compound present in mammalian brain suggested as a putative neurotransmitter, which has been shown to affect several aspects of dependence from various classes of drugs of abuse. In the present study, two sets of experiments were performed to investigate the effects of acute pretreatment with GHB on intravenous cocaine self-administration in rats. In the first experiment GHB was administered intragastrically at the doses of 175, 350, and 700 mg/kg to Long-Evans rats trained to self-administer cocaine using nose-poke as operandum. In the second experiment, GHB was administered intraperitoneally at the doses of 100, 200, and 400 mg/kg to Wistar rats trained to self-administer cocaine intravenously using lever-pressing as operandum. In both experiments acute pretreatment with GHB significantly and dose dependently reduced cocaine self-administration. The effectiveness of GHB was similar in both experiments, indicating that the effect of GHB on cocaine self- administration is independent of animal strain, route of administration, and type of operant response required. These results indicate that GHB reduces cocaine-seeking behavior in rats, modulating the acute reinforcing effect of cocaine. The clinical effectiveness of GHB in dependence from various classes of abused drugs warrants further studies to evaluate the possibility that GHB might represent a useful therapeutic agent for cocaine addiction in humans.

Original languageEnglish
Pages (from-to)697-702
Number of pages6
JournalPharmacology, Biochemistry and Behavior
Issue number3
Publication statusPublished - Mar 1998



  • Cocaine
  • Dependence
  • Gamma-hydroxybutyric acid
  • Intravenous self- administration
  • Rats

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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