MDMA and fenfluramine reduce L‐DOPA‐induced dyskinesia via indirect 5‐HT1A receptor stimulation
Christopher Bishop, Jennifer L. Taylor, Donald M. Kuhn, Karen L. Eskow, John Y. Park, Paul D. Walker
European Journal of Neuroscience May 1, 2006 DOI: 10.1111/j.1460-9568.2006.04790.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Sprague–Dawley rats with unilateral 6-hydroxydopamine medial forebrain bundle lesions |
| Interventions | benserazide MDMA fenfluramine WAY100635 |
| Dose | L-DOPA 12 mg/kg, benserazide 15 mg/kg, MDMA 0.25 or 2.5 mg/kg, fenfluramine 0.25 or 2.5 mg/kg, WAY100635 0.5 mg/kg |
| Duration | 1 week of daily L-DOPA treatment, with additional test sessions every 3rd or 4th day thereafter |
| Topics | MDMA Serotonin |
| Keywords | Benserazide Medial forebrain bundle Dyskinesia Fenfluramine Pharmacology Dopamine 5-HT Receptor Antagonist Levodopa Endocrinology |
| Citations | 63 |
| Key findings | Pretreatment with MDMA or fenfluramine reduced L-DOPA-induced abnormal involuntary movements in rats, an effect reversed by a 5-HT1A antagonist, indicating that stimulation of 5-HT1A receptors contributes to the antidyskinetic properties of these serotonin-augmenting compounds. |
Abstract
Abstract Chronic l ‐3,4‐dihydroxyphenylalanine (L‐DOPA) pharmacotherapy in Parkinson's disease is often accompanied by the development of abnormal and excessive movements known as dyskinesia. Clinical and experimental studies indicate that indirect serotonin agonists can suppress dyskinesia without affecting the efficacy of L‐DOPA. While the mechanism by which these effects occur is not clear, recent research suggests that serotonin 5‐HT1A receptors may play a pivotal role. To test this, male Sprague–Dawley rats with unilateral 6‐hydroxydopamine medial forebrain bundle lesions received 1 week of daily treatment with L‐DOPA (12 mg/kg, i.p.) plus benserazide (15 mg/kg, i.p.). Beginning on the 8th day of treatment and every 3rd or 4th day thereafter, rats were pretreated with vehicle (0.9% NaCl), the serotonin and dopamine releaser 3,4‐methylenedioxymethamphetamine (MDMA; 0.25 or 2.5 mg/kg, i.p.) or the serotonin releaser fenfluramine (FEN; 0.25 or 2.5 mg/kg, i.p.) 5 min prior to L‐DOPA, after which abnormal involuntary movements (AIMs) and rotations were quantified every 20th minute for 2 h. Pretreatment with 2.5 mg/kg of either MDMA or FEN reduced AIMs. To determine the contribution of the 5‐HT1A receptor to these effects, another group of L‐DOPA‐primed 6‐hydroxydopamine‐lesioned rats were pretreated with the 5‐HT1A antagonist WAY100635 (0.5 mg/kg, i.p.), MDMA + WAY100635 (2.5 + 0.5 mg/kg, i.p.) or FEN + WAY100635 (2.5 + 0.5 mg/kg, i.p.) 5 min prior to L‐DOPA and subsequent AIMs and rotation tests. The antidyskinetic effects of MDMA and FEN were reversed by cotreatment with WAY100635. These results suggest that 5‐HT‐augmenting compounds such as MDMA and FEN probably convey antidyskinetic properties in part via stimulation of 5‐HT1A receptors.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) EnantiomersIn Vitroand in the MPTP-Lesioned Primate:R-MDMA Reduces Severity of Dyskinesia, WhereasS-MDMA Extends Duration of ON-Time Journal of Neuroscience May 11, 2011
- Synthesis of R- and S-MDMA via nucleophilic ring-opening of homochiral N-tosylaziridines Australian Journal of Chemistry July 11, 2023
- Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats. Pharmacology, Biochemistry, and Behavior August 17, 2008
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