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Behavioral effects and pharmacokinetics of gamma-hydroxybutyrate (GHB) precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) in baboons.
- Source :
-
Psychopharmacology [Psychopharmacology (Berl)] 2009 Jun; Vol. 204 (3), pp. 465-76. Date of Electronic Publication: 2009 Feb 06. - Publication Year :
- 2009
-
Abstract
- Rationale: Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are prodrugs for gamma-hydroxybutyrate (GHB). Like GHB, GBL and 1,4-BD are drugs of abuse, but their behavioral effects may differ from GHB under some conditions.<br />Objectives: The first study compared the behavioral effects of GBL (32-240 mg/kg) and 1,4-BD (32-240 mg/kg) with each other and to effects previously reported for GHB (32-420 mg/kg). A second study determined GHB pharmacokinetics following intragastric administration of GHB, GBL, and 1,4-BD.<br />Methods: Operant responding for food, observed behavioral effects, and a fine-motor task occurred at multiple time intervals after administration of drug or vehicle. In a separate pharmacokinetics study, blood samples were collected across multiple time points after administration of GHB, GBL, and 1,4-BD.<br />Results: Like GHB, GBL, and 1,4-BD impaired performance on the fine-motor task, but the onset of motor impairment differed across drugs. GBL and 1,4-BD dose dependently decreased the number of food pellets earned, but at lower doses than previously observed for GHB. Similar to GHB, both GBL and 1,4-BD produced sedation, muscle relaxation, gastrointestinal symptoms, and tremors/jerks. Administration of GBL and 1,4-BD produced higher maximum concentrations of GHB with shorter times to maximum concentrations of GHB in plasma when compared to GHB administration.<br />Conclusions: GBL and 1,4-BD produced behavioral effects similar to those previously reported with GHB and the time course of effects were related to blood levels of GHB. Given their higher potency and faster onset of effects, the abuse liability of GBL and 1,4-BD may be greater than GHB.
- Subjects :
- Animals
Area Under Curve
Conditioning, Operant drug effects
Dose-Response Relationship, Drug
Food
Male
Motor Skills drug effects
Papio
Reward
Substance-Related Disorders psychology
4-Butyrolactone pharmacokinetics
4-Butyrolactone pharmacology
Behavior, Animal drug effects
Butylene Glycols pharmacokinetics
Butylene Glycols pharmacology
GABA Modulators pharmacokinetics
GABA Modulators pharmacology
Prodrugs pharmacokinetics
Prodrugs pharmacology
Sodium Oxybate pharmacokinetics
Sodium Oxybate pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2072
- Volume :
- 204
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19198808
- Full Text :
- https://doi.org/10.1007/s00213-009-1477-8