Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine.
Jeremy I Webster, David N. Harper, Susan Schenk
Behavioural Pharmacology June 1, 2017 DOI: 10.1097/fbp.0000000000000282 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study in rats Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA Fluoxetine Clomipramine meta-Chlorophenylpiperazine 8-OH-DPAT RU-24969 2 5-Dimethoxy-4-iodoamphetamine Amphetamine Apomorphine |
| Dose | MDMA 1.5 or 3.0 mg/kg; fluoxetine 0.3-3 mg/kg; clomipramine 1-10 mg/kg; meta-chlorophenylpiperazine 0.3-2 mg/kg; 8-OH-DPAT 0.03-0.3 mg/kg; RU-24969 0.3-3 mg/kg; 2,5-dimethoxy-4-iodoamphetamine 0.3-3 mg/kg; amphetamine 0.25 and 0.5 mg/kg; apomorphine 0.125 and 0.25 mg/kg |
| Topics | Serotonin MDMA |
| Keywords | Animals Rats, sprague-dawley Dopamine N-methyl-3,4-methylenedioxyamphetamine Hallucinogens Ligands Discrimination learning Reinforcement schedule Dose-response relationship, drug Male |
| Key points | Serotonergic drugs such as fluoxetine, clomipramine, and meta-chlorophenylpiperazine substituted for the 1.5 mg/kg MDMA cue but not the 3.0 mg/kg cue, whereas the dopaminergic drugs amphetamine and apomorphine substituted only for the 3.0 mg/kg cue. The authors suggest that serotonin and dopamine play differing roles in the discriminative stimulus effects of low versus higher doses of MDMA. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 5
- No Influence of Dopamine System Gene Variations on Acute Effects of MDMA Frontiers in Psychiatry October 24, 2019
- Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats Behavioural Pharmacology June 1, 2020
- Dopamine and serotonin antagonists fail to alter the discriminative stimulus properties of ±methylenedioxymethamphetamine Behavioural Pharmacology June 1, 2019
- Evaluating the abuse potential of psychedelic drugs as part of the safety pharmacology assessment for medical use in humans. Neuropharmacology November 2018
- “Ecstasy” to Addiction: Mechanisms and Reinforcing Effects of Three Synthetic Cathinone Analogs of MDMA Neuropharmacology January 31, 2018
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