title: Self-administration of gamma-hydroxybutyric acid (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons.
abstract: BACKGROUND
  Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are gamma-hydroxybutyrate (GHB) pro-drugs and drugs of abuse.
  
  
  OBJECTIVE
  Given the reports of abuse, and the ease at which GBL and 1,4-BD may be obtained, we investigated the reinforcing effects of GBL (n = 5) and 1,4-BD (n = 4) in baboons using IV self-administration procedures.
  
  
  METHODS
  Sessions ran 24 h/day. Each injection was contingent upon completion of a fixed number (120 or 160) of lever responses. A 3-h timeout period followed each injection, limiting the total number of injections to eight per day. Self-administration was first established with cocaine (0.32 mg/kg/injection). GBL (10-130.0 mg/kg/injection), 1,4-BD (10-100 mg/kg/injection), or vehicle was substituted for cocaine for at least 15 days. Food pellets were available ad libitum 24 h/day and were contingent upon completion of ten lever responses.
  
  
  RESULTS
  GBL (32-100 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in four of five baboons, and the mean rates of injection were high (more than six per day) in three baboons and moderate in the fourth baboon (four to six per day). 1,4-BD (78-130 mg/kg/injection) maintained significantly greater numbers of injections when compared to vehicle in only two out of four baboons, and mean rates were moderate to high in both baboons. Self-injection of these doses of GBL and 1,4-BD generally inhibited food-maintained responding.
  
  
  CONCLUSIONS
  GBL and 1,4-BD have abuse liability. Given that GBL and 1,4-BD are self-administered, are easier to obtain than GHB, and are detected in seized samples, additional legal control measures of these GHB pro-drugs may be needed.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Behavioral Biology Research Center, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Goodwin
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Kaminski
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
mesh_terms: D015107:4-Butyrolactone / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002072:Butylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000009:adverse effects*; D007275:Injections, Intravenous; D008297:Male; D010215:Papio; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D002072:Butylene Glycols; D006885:Hydroxybutyrates; D011355:Prodrugs; C111420:4-hydroxybutyric acid; C039681:1,4-butanediol; D003042:Cocaine; D015107:4-Butyrolactone