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Titolo:
Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA ('ecstasy') on the 5-HT and dopamine concentrations in mouse brain
Autore:
OShea, E; Esteban, B; Camarero, J; Green, AR; Colado, MI;
Indirizzi:
Univ Complutense Madrid, Fac Med, Dept Farmacol, Madrid 28040, Spain Univ Complutense Madrid Madrid Spain 28040 Farmacol, Madrid 28040, Spain De Montfort Univ, Sch Pharm & Pharmaceut Sci, Leicester LE1 9RH, Leics, England De Montfort Univ Leicester Leics England LE1 9RH LE1 9RH, Leics, England
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 1, volume: 40, anno: 2001,
pagine: 65 - 74
SICI:
0028-3908(2001)40:1<65:EOG1AF>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED SEROTONIN DEFICITS; RELEASE IN-VIVO; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; RAT-BRAIN; METHYLENEDIOXYMETHAMPHETAMINE MDMA; UPTAKE INHIBITORS; SUBSTITUTED AMPHETAMINES; MONOAMINERGIC SYSTEMS; INDUCED NEUROTOXICITY; SUPEROXIDE-DISMUTASE;
Keywords:
3,4-methylenedioxymethamphetamine; MDMA; ecstasy; GBR 12909; fluoxetine; dopamine; 5-hydroxytryptamine; neuroprotection; hyperthermia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Colado, MI Univ Complutense Madrid, Fac Med, Dept Farmacol, Madrid 28040, Spain Univ Complutense Madrid Madrid Spain 28040 adrid 28040, Spain
Citazione:
E. O'Shea et al., "Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA ('ecstasy') on the 5-HT and dopamine concentrations in mouse brain", NEUROPHARM, 40(1), 2001, pp. 65-74

Abstract

We examined the long term effect of 3,4 methylenedioxymethamphetamine (MDMA, 10, 20 and 30 mg/kg, i.p.) on the cerebral 5-hydroxytryptamine (5-HT) and dopamine content in Swiss Webster mice. Three injections of MDMA (20 or 30 mg/kg, i.p.) given 3 h apart produced a marked depletion in the striatal content of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) 7 days later. None of the doses administered altered the concentration of 5-HT or its metabolite 5-hydroxyindoleaceticacid (5-HIAA) in several brain areas. Pre-treatment with the dopamine uptake inhibitor GBR 12909 (10 mg/kg, i.p.), 30 min before each of the three MDMA (30 mg/kg, i.p.) injections, completely prevented the long term loss in the striatal catechol concentrations. However, GBR 12909 (10 mg/kg, i.p.) not only failed to prevent the acute effects induced by MDMA (30 mg/kg x 3, i.p.) on dopamine metabolism 30 min later, but in fact potentiated them. The 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i.p.) failed to prevent boththe acute and long term dopaminergic deficits. MDMA (30 mg/kg x 3) alteredthe body temperature of the mice biphasically, producing a rapid hyperthermia followed by prolonged hypothermia. In contrast, MDMA (20 mg/kg x 3) produced an initial hypothermia followed by hyperthermia. The present experiments therefore appear to rule out any direct relationship between the neurotoxic effects of MDMA and its acute effects on body temperature in mice. Fluoxetine administered 30 min before each MDMA (30 mg/kg) injection preventedthese temperature changes, while GBR 12909 was without effect. This suggests that the neuroprotective effect of GBR 12909 against MDMA-induced neurotoxicity is not directly related to its ability to inhibit the MDMA-induced acute effects on dopamine metabolism or alter the MDMA-induced temperature change. The data illustrate major differences in the neurotoxic profile of MDMA in mice and rats. (C) 2000 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 06:34:36