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-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.
Quang
Lawrence S
LS
Division of Pediatric Pharmacology & Critical Care, Rainbow Babies & Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA. lawrence.quang@case.edu
Colombo
Giancarlo
G
Lobina
Carla
C
Maccioni
Paola
P
Orru
Alessandro
A
Gessa
Gian Luigi
GL
Maher
Timothy J
TJ
Carai
Mauro A M
MA
D015107:4-Butyrolactone / Q000009:adverse effects*; D000818:Animals; D001522:Behavior, Animal; D002072:Butylene Glycols / Q000009:adverse effects*; D005260:Female; D006885:Hydroxybutyrates / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000209:etiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D002072:Butylene Glycols; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D015107:4-Butyrolactone