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Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine.
Behav Pharmacol. 2017 06; 28(4):245-254.BP

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+Show Affiliations

Faculty of Science, School of Psychology, Victoria University of Wellington, Wellington, New Zealand.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27922542

Citation

Webster, Jeremy I., et al. "Generalization of Serotonin and Dopamine Ligands to the Discriminative Stimulus Effects of Different Doses of ±3,4-methylenedioxymethamphetamine." Behavioural Pharmacology, vol. 28, no. 4, 2017, pp. 245-254.
Webster JI, Harper DN, Schenk S. Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine. Behav Pharmacol. 2017;28(4):245-254.
Webster, J. I., Harper, D. N., & Schenk, S. (2017). Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine. Behavioural Pharmacology, 28(4), 245-254. https://doi.org/10.1097/FBP.0000000000000282
Webster JI, Harper DN, Schenk S. Generalization of Serotonin and Dopamine Ligands to the Discriminative Stimulus Effects of Different Doses of ±3,4-methylenedioxymethamphetamine. Behav Pharmacol. 2017;28(4):245-254. PubMed PMID: 27922542.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine. AU - Webster,Jeremy I, AU - Harper,David N, AU - Schenk,Susan, PY - 2016/12/7/pubmed PY - 2018/3/7/medline PY - 2016/12/7/entrez SP - 245 EP - 254 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 28 IS - 4 N2 - 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. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/27922542/Generalization_of_serotonin_and_dopamine_ligands_to_the_discriminative_stimulus_effects_of_different_doses_of_±34_methylenedioxymethamphetamine_ L2 - https://doi.org/10.1097/FBP.0000000000000282 DB - PRIME DP - Unbound Medicine ER -