PMID- 16817869
OWN - NLM
STAT- MEDLINE
DCOM- 20060804
LR  - 20131121
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 23
IP  - 10
DP  - 2006 May
TI  - MDMA and fenfluramine reduce L-DOPA-induced dyskinesia via indirect 5-HT1A 
      receptor stimulation.
PG  - 2669-76
AB  - 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.
FAU - Bishop, Christopher
AU  - Bishop C
AD  - Behavioural Neuroscience Program, Department of Psychology, State University of 
      New York at Binghamton, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA. 
      cbishop@binghamton.edu
FAU - Taylor, Jennifer L
AU  - Taylor JL
FAU - Kuhn, Donald M
AU  - Kuhn DM
FAU - Eskow, Karen L
AU  - Eskow KL
FAU - Park, John Y
AU  - Park JY
FAU - Walker, Paul D
AU  - Walker PD
LA  - eng
GR  - NS39013/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Adrenergic Agents)
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Serotonin 5-HT1 Receptor Antagonists)
RN  - 0 (Serotonin Agents)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 2DS058H2CF (Fenfluramine)
RN  - 46627O600J (Levodopa)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic Agents/toxicity
MH  - Animals
MH  - Antiparkinson Agents/adverse effects
MH  - Chromatography, High Pressure Liquid
MH  - Dose-Response Relationship, Drug
MH  - Dyskinesia, Drug-Induced/*prevention & control
MH  - Fenfluramine/*therapeutic use
MH  - Levodopa/adverse effects
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*therapeutic use
MH  - Oxidopamine/toxicity
MH  - Parkinsonian Disorders/chemically induced/*drug therapy
MH  - Rats
MH  - Receptor, Serotonin, 5-HT1A/*drug effects
MH  - Serotonin 5-HT1 Receptor Antagonists
MH  - Serotonin Agents/*therapeutic use
EDAT- 2006/07/05 09:00
MHDA- 2006/08/05 09:00
CRDT- 2006/07/05 09:00
PHST- 2006/07/05 09:00 [pubmed]
PHST- 2006/08/05 09:00 [medline]
PHST- 2006/07/05 09:00 [entrez]
AID - EJN4790 [pii]
AID - 10.1111/j.1460-9568.2006.04790.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2006 May;23(10):2669-76. doi: 10.1111/j.1460-9568.2006.04790.x.