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MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation.
Eur J Neurosci. 2006 May; 23(10):2669-76.EJ

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.

Authors+Show Affiliations

Behavioural Neuroscience Program, Department of Psychology, State University of New York at Binghamton, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA. cbishop@binghamton.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16817869

Citation

Bishop, Christopher, et al. "MDMA and Fenfluramine Reduce L-DOPA-induced Dyskinesia Via Indirect 5-HT1A Receptor Stimulation." The European Journal of Neuroscience, vol. 23, no. 10, 2006, pp. 2669-76.
Bishop C, Taylor JL, Kuhn DM, et al. MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation. Eur J Neurosci. 2006;23(10):2669-76.
Bishop, C., Taylor, J. L., Kuhn, D. M., Eskow, K. L., Park, J. Y., & Walker, P. D. (2006). MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation. The European Journal of Neuroscience, 23(10), 2669-76.
Bishop C, et al. MDMA and Fenfluramine Reduce L-DOPA-induced Dyskinesia Via Indirect 5-HT1A Receptor Stimulation. Eur J Neurosci. 2006;23(10):2669-76. PubMed PMID: 16817869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A receptor stimulation. AU - Bishop,Christopher, AU - Taylor,Jennifer L, AU - Kuhn,Donald M, AU - Eskow,Karen L, AU - Park,John Y, AU - Walker,Paul D, PY - 2006/7/5/pubmed PY - 2006/8/5/medline PY - 2006/7/5/entrez SP - 2669 EP - 76 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 23 IS - 10 N2 - 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. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16817869/MDMA_and_fenfluramine_reduce_L_DOPA_induced_dyskinesia_via_indirect_5_HT1A_receptor_stimulation_ DB - PRIME DP - Unbound Medicine ER -