Evaluation for the withdrawal syndrome from gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) in different rat lines

A severe and life-threatening gamma y-hydroxybutyric acid (GHB) withdrawal syndrome, clinically similar to the alcohol withdrawal syndrome, is increasingly being reported in GHB addicts. We investigated for the occurrence of withdrawal in Wistar and Sprague-Dawley rats, and in the selectively bred lines of GHB-sensitive (GHB-S) and Sardinian alcohol-preferring (sP) rats, following chronic administration of GHB, gamma-butyrolactone (GBL), and/or 1,4-butanediol (1,4-BD). Using validated rodent alcohol withdrawal scoring scales, little to no spontaneous or pharmacologically precipitated withdrawal effects were observed in Wistar, Sprague-Dawley, or GHB-S rats. Conversely, sP rats displayed both spontaneous and precipitated audiogenic seizures following abrupt cessation of chronic GHB or 1,4-BD administration and following pharmacological challenge with the GABA(B) receptor-selective antagonist, SCH 50911, respectively.