Chronic 1,4-butanediol treatment in rats: cross-tolerance to gamma-hydroxybutyrate and (+/-)-baclofen.
The effects of 1,4-butanediol, gamma-hydroxybutyrate (GHB), and (+/-)-baclofen on food-maintained responding in rats were assessed before, during, and after chronic treatment with 1,4-butanediol. Six weeks of treatment with 1,4-butanediol (twice daily, 320 mg/kg for 3 weeks followed by 560 mg/kg for 3 weeks) decreased sensitivity to the rate-decreasing effects of (+/-)-baclofen and GHB without changing sensitivity to 1,4-butanediol. Sensitivity to (+/-)-baclofen and GHB returned to control values 2-3 weeks after discontinuation of treatment. These data suggest that tolerance to the effects of GHB or its precursors might result from changes in GABA(B) mechanisms.
Eckermann
Kary A
KA
Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Koek
Wouter
W
France
Charles P
CP
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002072:Butylene Glycols / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D012978:Sodium Oxybate / Q000494:pharmacology*
D002072:Butylene Glycols; D012978:Sodium Oxybate; C039681:1,4-butanediol; D001418:Baclofen