S(+)- and R(−)N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) as discriminative stimuli: Effect of cocaine
Section snippets
Materials and methods
Seventeen male Sprague–Dawley rats (Charles River Laboratories), weighing 250–300 g at the beginning of the study, were trained to discriminate (15-min presession injection interval) doses of S(+)MDMA (n = 10) or R(−)MDMA (n = 7) from saline vehicle (sterile 0.9% saline) under a variable interval 15-s schedule of reinforcement for sweetened condensed milk reward using standard two-lever Coulbourn Instruments operant equipment as previously described for (±)MDMA (Glennon and Young, 2000). Animal
Training
The study began with S(+)- and R(−)MDMA training doses of 0.75 mg/kg versus saline vehicle. In the S(+)MDMA-training group, 2 months of training at that dose followed by 1 month of training at 1 mg/kg did not result in consistent responding under the drug (i.e., ≥ 80% drug-appropriate responding) or saline (i.e., ≤ 20% drug-appropriate responding) conditions. After 2 to 3 weeks of additional training at 1.5 mg/kg of S(+)MDMA, however, the animals reliably learned the discrimination (Fig. 1).
Fig. 2
Discussion
Racemic MDMA has been used as a training stimulus in numerous drug discrimination studies and a typical training dose is 1.5 mg/kg; hence, the racemate training dose consists of 0.75 mg/kg of S(+)MDMA and 0.75 mg/kg of R(−)MDMA. S(+)MDMA is thought to be the more potent enantiomer of MDMA and it was expected that 0.75 mg/kg of this isomer would function as a discriminative stimulus. This was found not to be the case and, at this time, a ready explanation is not apparent. In the present study,
Acknowledgment
This work was supported in part by PHS grant DA-01642.
References (45)
- et al.
Increasing the selectivity of drug discrimination procedures
Pharmacol Biochem Behav
(1999) - et al.
Assessment of MDA and MDMA optical isomers in a stimulant-hallucinogen discrimination
Pharmacol Biochem Behav
(1997) - et al.
Time course and discriminative stimulus effects of the optical isomers of 3,4-methylenedioxymethamphetamine (MDMA)
Pharmacol Biochem Behav
(1997) - et al.
Self-administration of methylenedioxymethamphetamine (MDMA) by rhesus monkeys
Drug Alcohol Depend
(1986) - et al.
Effect of SCH 23390 on (±)-3,4-methylenedioxymethamphetamine hyperactivity and self-administration in rats
Pharmacol Biochem Behav
(2004) - et al.
Discriminative stimulus properties of (±)methylenedioxymethamphetamine and (±)methylenedioxyamphetamine in pigeons
Drug Alcohol Depend
(1986) - et al.
Further investigation of the discriminative stimulus properties of MDA
Pharmacol Biochem Behav
(1984) - et al.
MDMA stimulus generalization to the 5-HT1A serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin
Pharmacol Biochem Behav
(2000) - et al.
The effects of MDMA (“Ecstasy”) and its optical isomers on schedule-controlled responding in mice
Pharmacol Biochem Behav
(1987) - et al.
Stimulus properties of 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) analogs
Pharmacol Biochem Behav
(1988)
The effect of the optical isomers of 3,4-methylenedioxymethamphetamine (MDMA) on stereotyped behavior in rats
Pharmacol Biochem Behav
The effects of (±)methylenedioxymethamphetamine and (±)methylenedioxyamphetamine in monkeys trained to discriminate (+)amphetamine from saline
Drug Alcohol Depend
Comparison of the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and cocaine: asymmetric generalization
Drug. Alcohol Depend
A comparison of the reinforcing efficacy of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) with cocaine in rhesus monkeys
Drug Alcohol Depend
Reaction of nitroolefins with Raney nickel and sodium hypophosphite. A mild method for converting into ketones (or aldehydes)
Tetrahedron Lett
The effect of R(−)HA966 or ACEA 1021 on dexfenfluramine or (S)-MDMA-induced changes in temperature, activity, and neurotoxicity
Pharmacol Biochem Behav
MDMA as a discriminative stimulus: isomeric comparisons
Pharmacol Biochem Behav
The subjective effects of MDMA and mCPP in moderate MDMA users
Drug Alcohol Depend
Psychological and cardiovascular effects and short-term sequelae of MDMA (“Ecstasy”) in MDMA-naïve healthy volunteers
Neuropsychopharmacology
Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
J Org Chem
Absolute configuration and psychotomimetic activity
NIDA Res Monogr
Assessment of the discriminative stimulus effects of the optical isomers of Ecstasy (3,4-methylenedioxymethamphetamine; MDMA)
Behav Pharmacol
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