Reinforcing effects of certain serotonin-releasing amphetamine derivatives.
Danuta Marona‐lewicka, G S Rhee, J E Sprague, D E Nichols
Pharmacology, Biochemistry, and Behavior January 1996 DOI: 10.1016/0091-3057(95)00205-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Freely moving rats |
| Interventions | MDMA MBDB fenfluramine MMAI |
| Dose | MDMA 5 and 10 mg/kg; MBDB 10 mg/kg; fenfluramine 4, 6, and 10 mg/kg; MMAI 1.25, 2.5, 5, 10, and 20 mg/kg |
| Measures | conditioned place preference paradigm, in vivo microdialysis |
| Topics | Serotonin |
| Key findings | MDMA and MBDB produced conditioned place preference in rats, with MDMA's effect stronger and dose-dependent, while fenfluramine and higher doses of MMAI produced place aversion. MDMA elevated extracellular dopamine and decreased DOPAC in the nucleus accumbens, but MBDB, fenfluramine, and MMAI did not, leading the authors to propose that dopaminergic activation may mediate MDMA-like reward. |
Abstract
The present study was designed to characterize further the rewarding and aversive properties of 3,4-methylenedioxymethamphetamine (MDMA), the alpha-ethyl homologue of MDMA (MBDB), fenfluramine, and the selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan (MMAI) using the conditioned place preference paradigm (CPP). Extracellular dopamine (DA) and its metabolite DOPAC were also measured in the nucleus accumbens after systemic drug administration, using in vivo microdialysis in freely moving rats. MDMA produced a positive dose-dependent effect in the CPP test, which was maximal at doses of 5 and 10 mg/kg. MBDB also induced a positive CPP, with a maximum effect at 10 mg/kg. The conditioning effect of MBDB was more than 2.5-fold weaker compared with MDMA. Fenfluramine evoked place aversion at doses of 4, 6, and 10 mg/kg. This effect of fenfluramine was independent of dose. MMAI at doses of 1.25, 2.5, and 5 mg/kg produced no significant effect on place conditioning. At doses of 10 and 20 mg/kg, MMAI produced an effect similar to fenfluramine: Place aversion was independent of dose. In the microdialysis experiments, MDMA significantly elevated extracellular DA and induced a decrease of DOPAC in the nucleus accumbens. Thus, activation of dopaminergic systems may be responsible for the rewarding properties of MDMA-like drugs. In contrast to the effects seen with MDMA, no difference in extracellular DA or DOPAC was seen after injection of MBDB, fenfluramine, or MMAI, even though MBDB weakly induced a place preference. The mechanism responsible for the development of place aversion by fenfluramine or MMAI is unknown at this time and requires further study.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 23
- Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys Behavioural Pharmacology March 1, 2004
- Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Pharmacology 2001
- Effects of acute social stress on the conditioned place preference induced by MDMA in adolescent and adult mice Behavioural Pharmacology September 1, 2014
- 5-Iodo-2-aminoindan (5-IAI): chemistry, pharmacology, and toxicology of a research chemical producing MDMA-like effects. Toxicology Letters March 27, 2013
- Age differences in (±) 3,4‐methylenedioxymethamphetamine (MDMA)‐induced conditioned taste aversions and monoaminergic levels Developmental Psychobiology June 15, 2013
and 18 more in the library
Cites 24
- Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens Journal of Psychoactive Drugs October 1, 1986
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
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