Catalepsy and Comparing Gamma-Hydroxybutyrate, 1,4-Butanediol, and Gamma-Butyrolactone

Gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) are known substances of abuse. As GHB prodrugs, 1,4-BD and GBL’s effects are expected to be similar to those of GHB. The acute and chronic effects of these three compounds were evaluated for cataleptic activity using equimolar doses in mice. The need of metabolic conversion into GHB for 1,4-BD and GBL influenced onset, time to the peak effect and duration of response. Tolerance development was also determined on days 6 and 14 and then challenged with a higher dose on day 15 in chronically pretreated mice. Chronic GHB produced tolerance to catalepsy, as the cataleptic responses on days 6 and 14 were significantly less than that of day 1 (p < 0.05). However, 1,4-BD and GBL were less prone to tolerance development. While, 1,4-BD and GBL share some of the effects of GHB (acute catalepsy), but not the development of tolerance.