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

Brain Res Brain Res Protoc. 2005 Jul;15(2):75-8. doi: 10.1016/j.brainresprot.2005.04.001.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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