Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine.
Studies that have attributed the discriminative stimulus effects of ±3,4-methylenedioxymethamphetamine (MDMA) to serotonergic mechanisms typically use a relatively low training dose of 1.5 mgkg. The role of serotonin in the discriminative stimulus effects of higher doses of MDMA is, however, unknown. Separate groups of rats were trained to discriminate MDMA (1.5 or 3.0 mgkg) from saline using a two-lever, food-reinforced drug-discrimination procedure. Generalization tests were carried out with a range of serotonin and dopamine ligands. Fluoxetine (0.3-3 mgkg), clomipramine (1-10 mgkg) and meta-chlorophenylpiperazine (0.3-2 mgkg) dose-dependently substituted for the 1.5 mgkg MDMA stimulus, but not the 3.0 mgkg MDMA stimulus. 8-OH-DPAT (0.03-0.3 mgkg) and RU-24969 (0.3-3 mgkg) substituted for both the low-dose and the high-dose MDMA stimulus. The generalization dose-effect curve produced by 2,5-dimethoxy-4-iodoamphetamine (0.3-3 mgkg) was shifted to the right for the 3.0 mgkg MDMA-trained group. Amphetamine (0.25 and 0.5 mgkg) and apomorphine (0.125 and 0.25 mgkg) substituted for the 3.0 mgkg, but not the 1.5 mgkg MDMA stimulus. The results suggest some differences in the role of serotonin and dopamine in the discriminative stimulus effects of a low versus a higher dose of MDMA.