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.