title: Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine.
abstract: 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 mg/kg. 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 mg/kg) 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 mg/kg), clomipramine (1-10 mg/kg) and meta-chlorophenylpiperazine (0.3-2 mg/kg) dose-dependently substituted for the 1.5 mg/kg MDMA stimulus, but not the 3.0 mg/kg MDMA stimulus. 8-OH-DPAT (0.03-0.3 mg/kg) and RU-24969 (0.3-3 mg/kg) 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 mg/kg) was shifted to the right for the 3.0 mg/kg MDMA-trained group. Amphetamine (0.25 and 0.5 mg/kg) and apomorphine (0.125 and 0.25 mg/kg) substituted for the 3.0 mg/kg, but not the 1.5 mg/kg 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.
authors.affiliation: Faculty of Science, School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Jeremy I
authors.initials: JI
authors.lastname: Webster
authors.forename: David N
authors.initials: DN
authors.lastname: Harper
authors.forename: Susan
authors.initials: S
authors.lastname: Schenk
mesh_terms: D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology; D008024:Ligands; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012701:Serotonin / Q000378:metabolism*
chemical_list: D006213:Hallucinogens; D008024:Ligands; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine