Tolerance to the hypnotic and electroencephalographic effect of gamma-hydroxybutyrate in the rat: pharmacokinetic and pharmacodynamic aspects

• Published in: Journal of pharmacy and pharmacology 2003-05, Vol.55 (5), p.609-615
• Main Authors: Van Sassenbroeck, Diederik K., de Paepe, Peter, Belpaire, Frans M., Boon, Paul A., Buylaert, Walter A.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Tolerance - physiology; Electroencephalography - drug effects; Hypnotics and Sedatives - pharmacology; Male; Medical sciences; Rats; Rats, Wistar; Sleep - drug effects; Sleep - physiology; Sodium Oxybate - blood; Sodium Oxybate - pharmacology
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/002235703765344513

Tolerance to gamma‐hydroxybutyrate (GHB) has been suggested in illicit users and has been described for the hypnotic effect in the rat. The aim of this study was to investigate whether tolerance is also observed for the EEG effect, and whether the EEG can give insight into the pharmacodynamic aspects of GHB tolerance. In three series of experiments, rats were pre‐treated with either the GHB precursor gamma‐butyrolactone (GBL) or saline intraperitoneally twice daily. In the first series, a reduction in sleeping time was observed in the GBL pre‐treated rats compared with controls. In the second series, a fast infusion of GHB (300 mg kg−1 over 5 min) was given after 10 days pre‐treatment. The GHB plasma concentration‐time curves showed a slightly faster decrease in GHB concentration in the GBL pre‐treated rats, suggesting a small induction of the GHB metabolism (Vmax = 2882 ± 457 μg min−1 kg−1 vs 2205 ± 315 μg min−1 kg−1, P