S(+)- and R(−) N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) as discriminative stimuli: Effect of cocaine

Abstract

Racemic N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (methylenedioxymethamphetamine, MDMA), a central stimulant and empathogenic agent, and cocaine are drugs of abuse that function as training drugs in drug discrimination studies. In tests of stimulus generalization (substitution), asymmetric generalization occurs between the two agents: a (±)MDMA stimulus generalized to cocaine, but a cocaine stimulus did not generalize to (±)MDMA. A possible explanation may be found, at least in part, in the stimulus effects of the optical isomers of MDMA. In the present study, groups of male Sprague–Dawley rats were trained to discriminate either S(+)MDMA (training dose = 1.5 mg/kg, i.p.; n = 10; ED 50 = 0.6 mg/kg) or R(−)MDMA (training dose = 1.75 mg/kg, i.p.; n = 7; ED 50 = 0.4 mg/kg) from saline vehicle using a VI-15s schedule of reinforcement. Tests of stimulus generalization with cocaine were conducted in each of the two groups. Cocaine only partially substituted for the S(+)MDMA stimulus (maximum = 39% drug-appropriate responding), and various doses of cocaine did not enhance the percent drug-appropriate responding produced by a low dose (0.5 mg/kg) of S(+)MDMA. In contrast, the R(−)MDMA stimulus generalized completely to cocaine (ED 50 = 1.3 mg/kg). Taken together with an earlier report that a (±)MDMA stimulus generalizes to cocaine, it would seem that the stimulus actions of cocaine might share greater similarity with R(−)MDMA than with S(+)MDMA.