title: 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.affiliation: Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari, Italy.
authors.forename: Mauro A M
authors.initials: MA
authors.lastname: Carai
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Quang
authors.forename: Sergio
authors.initials: S
authors.lastname: Atzeri
authors.forename: Carla
authors.initials: C
authors.lastname: Lobina
authors.forename: Paola
authors.initials: P
authors.lastname: Maccioni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Orrù
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Maher
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
mesh_terms: D000818:Animals; D002072:Butylene Glycols / Q000494:pharmacology*; D004195:Disease Models, Animal; D058788:GABA-B Receptor Antagonists; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000401:mortality / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000401:mortality / Q000503:physiopathology*
chemical_list: C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D002072:Butylene Glycols; D058788:GABA-B Receptor Antagonists; D006885:Hydroxybutyrates; D009025:Morpholines; C111420:4-hydroxybutyric acid; C039681:1,4-butanediol