Withdrawal syndrome from gamma-hydroxybutyric acid (GHB) and 1,4-butanediol (1,4-BD) in Sardinian alcohol-preferring rats.

Abstract

Gamma-hydroxybutyric acid (GHB) and its precursors, 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), are recreational drugs widely abused in the US, Europe and Australasia. A severe withdrawal syndrome from GHB, 1,4-BD and GBL has been increasingly documented over the last years, necessitating the development of a reliable animal model for investigations of potential therapeutic approaches. The present study describes the induction and occurrence of audiogenic seizures as a sign of withdrawal from GHB and 1,4-BD in selectively bred Sardinian alcohol-preferring (sP) rats, treated with escalating doses of GHB (1.5-3.5 g/kg, twice daily; i.g.) or 1,4-BD (500-1000 mg/kg, twice daily; i.g.) for 9 consecutive days. Acute administration of the selective GABA(B) receptor antagonist, SCH 50911, dramatically increased seizure occurrence. We propose that the inherent sensitivity of sP rats to different GHB-associated responses may have contributed to the unraveling of a phenomenon which was otherwise not recognizable in other rat strains.

• Authors: Mauro A M Carai, Lawrence S Quang, Sergio Atzeri, Carla Lobina, Paola Maccioni, Alessandro Orrù, Gian Luigi Gessa, Timothy J Maher, Giancarlo Colombo
• Journal: Brain research. Brain research protocols (Brain Res Brain Res Protoc) Vol. 15 Issue 2 Pg. 75-8 (Jul 2005) ISSN: 1385-299X [Print] Netherlands
• PMID: 15886053 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid
• Butylene Glycols
• GABA-B Receptor Antagonists
• Hydroxybutyrates
• Morpholines
• 4-hydroxybutyric acid
• 1,4-butanediol

Topics

• Animals
• Butylene Glycols (pharmacology)
• Disease Models, Animal
• GABA-B Receptor Antagonists
• Hydroxybutyrates (pharmacology)
• Male
• Morpholines (pharmacology)
• Rats
• Rats, Inbred Strains
• Substance Withdrawal Syndrome (mortality, physiopathology)
• Substance-Related Disorders (mortality, physiopathology)