Prior exposure to methylenedioxyamphetamine (MDA) induces serotonergic loss and changes in spontaneous exploratory and amphetamine-induced behaviors in rats.
Andrew Harkin, Thomas J. Connor, J Mulrooney, J P Kelly, Brian E. Leonard
Life Sciences February 9, 2001 DOI: 10.1016/s0024-3205(00)01039-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Population | Adult male Sprague Dawley rats |
| Interventions | MDA d-amphetamine |
| Dose | MDA 7.5 mg/kg i.p. twice daily; d-amphetamine 12 mg/kg i.p. |
| Duration | Four days of MDA dosing, with testing four weeks after the last dose |
| Measures | automated video registration and computer interpretation of open field behavior, [3H] paroxetine binding, 5-HT concentrations |
| Topics | Serotonin |
| Key findings | Rats given repeated MDA showed reduced exploratory locomotion and rearing and increased grooming four weeks later, plus an enhanced locomotor and stereotyped response to d-amphetamine. Brain 5-HT fell 20-30% in several regions and cortical [3H] paroxetine binding fell 40%, which the authors interpret as serotonergic nerve terminal loss and propose as a behavioral model of MDA-induced serotonergic deficit. |
Abstract
The substituted amphetamine 3,4 methylenedioxyamphetamine (MDA) is a popular recreational drug of abuse. Administration of MDA to experimental animals has been shown to induce damage to serotonergic axons and nerve terminals. However, there is a lack of information on whether these treatments can produce any long-term changes in behavioural performance particularly under stressful conditions. In the present study, MDA (7.5 mg/kg; i.p.) was administered twice daily to adult male Sprague Dawley rats for four days. Four weeks following the last dose, spontaneous behaviors of these animals were tracked and scored in a novel "open field" environment using an automated video registration and computer interpretation system. Changes in behavior were observed in MDA treated animals including reductions in exploratory oriented behaviors (locomotion and rearing) and increases in grooming behavior when compared to vehicle treated controls. MDA-treated animals also displayed an enhanced locomotor and stereotyped response to d-amphetamine (12 mg/kg; i.p.). Significant reductions in 5-HT concentrations (20-30%) were observed in the frontal cortex, amygdala, striatum, and hypothalamus as a result of MDA treatment. In addition, [3H] paroxetine binding was reduced by (40%) in the cortex of MDA treated rats indicating that the decrease in 5-HT concentrations were accompanied by a reduction in intact presynaptic 5-HT nerve terminals. Changes in behavioural performance in a novel "open field" environment and following d-amphetamine challenge might be considered as a behavioural model of serotonergic deficit induced by MDA. The findings of this study also suggest that MDA use may increase both the abuse potential, and the propensity to develop psychosis as a result of abusing other psychostimulants such as d-amphetamine.
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 10
- MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology Current Neuropharmacology August 1, 2013
- Mechanisms mediating the ability of caffeine to influence MDMA (‘Ecstasy’)‐induced hyperthermia in rats British Journal of Pharmacology May 24, 2010
- Persistent cerebrovascular effects of MDMA and acute responses to the drug European Journal of Neuroscience July 1, 2006
- Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging International Journal of Molecular Sciences June 24, 2022
- Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination. Psychopharmacology August 21, 2010
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