PMID: 7539115Dec 1, 1994Paper

Chlormethiazole, dizocilpine and haloperidol prevent the degeneration of serotonergic nerve terminals induced by administration of MDMA ('Ecstasy') to rats

Neuropharmacology
K E Hewitt, A R Green

Abstract

An investigation has been made into the effect of 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') administration on the concentration of 5-hydroxytryptamine (5-HT), uptake of [3H]5-HT and [3H]paroxetine binding in rat cerebral cortex tissue. Four days after 2 injections of MDMA (20 mg/kg i.p., 6 hr apart) the concentrations of 5-HT and its metabolite 5-HIAA were reduced by 60%. The binding of [3H]paroxetine to the presynaptic 5-HT transporter was decreased and high affinity uptake of [3H]5-HT was reduced by a similar amount, indicating neurodegeneration of 5-HT terminals. Pretreatment with chlormethiazole (100 mg/kg i.p.), 10 min before each MDMA injection prevented the decrease in both [3H]parotextine binding and uptake of [3H]5-HT. The loss in 5-HT and 5-HIAA content was also attenuated. Pretreatment with dizocilpine (1 mg/kg i.p.) or haloperidol (2 mg/kg i.p.) also prevented the MDMA-induced loss of [3H]paroxetine binding and attenuated the loss of 5-HT and 5-HIAA content. All three compounds also decreased the degree of hyperthermia that follows MDMA administration, although previous studies suggest that the long term neurodegeneration is not associated with the acute hyperthermic response. These data support the find...Continue Reading

Citations

Apr 15, 2004·Psychopharmacology·M Isabel ColadoA Richard Green
Apr 18, 2009·Molecular Neurobiology·João Paulo CapelaFélix Carvalho
Dec 1, 1994·Progress in Neurobiology·A R Green, A J Cross
Apr 1, 1997·Pharmacology, Biochemistry, and Behavior·S ThaminyD Bentué-Ferrer
May 24, 2001·Progress in Neuro-psychopharmacology & Biological Psychiatry·E D O'LoinsighK M O'Boyle
Feb 23, 2010·PloS One·Clara TouriñoOlga Valverde
Jul 21, 2009·European Journal of Pharmacology·Alinde E WallingaBauke Buwalda
May 27, 2008·British Journal of Pharmacology·J R Docherty
Jun 14, 2006·British Journal of Pharmacology·Esther O'SheaMaria Isabel Colado
Oct 7, 2004·European Journal of Pharmacology·A Richard GreenM Isabel Colado

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