ArticlesTime Course Analysis of the Discriminative Stimulus Effects of the Optical Isomers of 3,4-Methylenedioxymethamphetamine (MDMA)
Section snippets
Subjects
Subjects were experimentally naive, male Sprague-Dawley rats (Harlan Breeding Laboratories, Indianapolis, IN), aged approximately 60 days at the beginning of the study. Animals were housed individually in wire-mesh cages in a colony maintained on a 12-h light (0700–1900)/12-h dark cycle and at a constant temperature (20–22°C). Water was provided ad libitum, and commercial rat chow was rationed to maintain animals at approximately 85% of their free feeding weights throughout the study.
Apparatus
Training
Results
Animals administered (+)-MDMA or saline 20 min prior to training sessions attained the discrimination criterion within a mean of 75 training sessions (range = 64–93), whereas animals administered (−)-MDMA or saline 20 min prior to training sessions acquired the discrimination criterion within a mean of 65 training sessions (range = 39–76). Animals administered (+)-MDMA or saline at a 90-min presession injection interval failed to attain the discrimination criterion, thus, substitution and
Experiment 2
Because (+)-MDMA did not successfully establish discriminative stimulus control when administered 90 min prior to training sessions, a second experiment was conducted to examine further the differences in the time course of the two MDMA isomers. Rats were trained to discriminate either (+)-MDMA or (−)-MDMA from saline, and substitution tests were administered with the training drugs at different presession injection intervals. So that comparisons could be made more easily between the dose
Results
Six of the eight subjects administered training sessions with (+)-MDMA (1.5 mg/kg) attained the discrimination criterion within an average of 48 training sessions (SD = 10.18; range = 37–66). Seven of the eight subjects administered training sessions with (−)-MDMA attained the discrimination criterion within an average of 50 training sessions (SD = 12.06; range = 37–66). One rat in each training group died early in the study before the discrimination criterion could be met. An additional rat in
Discussion
The ability of MDMA to establish and maintain discriminative stimulus control over lever-pressing behavior of rats was first demonstrated by Glennon et al. in 1986 [13]. Schechter [25]subsequently demonstrated that both of the MDMA enantiomers substitute for the racemate. Several reports followed that described attempts to characterize the discriminative stimulus effects of the MDMA isomers by testing these agents in animals trained to discriminate other drugs such as psychostimulants 4, 14, 22
Acknowledgements
We thank Dr. William Potter for his expert technical assistance in the computer programming of experimental events and data collection.
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