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Titolo:
BRAIN DOPAMINE NEUROTOXICITY IN BABOONS TREATED WITH DOSES OF METHAMPHETAMINE COMPARABLE TO THOSE RECREATIONALLY ABUSED BY HUMANS - EVIDENCE FROM [C-11] WIN-35,428 POSITRON-EMISSION-TOMOGRAPHY STUDIES AND DIRECT IN-VITRO DETERMINATIONS
Autore:
VILLEMAGNE V; YUAN J; WONG DF; DANNALS RF; HATZIDIMITRIOU G; MATHEWS WB; RAVERT HT; MUSACHIO J; MCCANN UD; RICAURTE GA;
Indirizzi:
JOHNS HOPKINS MED INST,DEPT NEUROL,5501 BAYVIEW DR,ROOM 5B71E BALTIMORE MD 21224 JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED BALTIMORE MD 21205 JOHNS HOPKINS MED INST,DEPT NEUROL BALTIMORE MD 21205 NIMH,UNIT ANXIETY DISORDERS,BIOL PSYCHIAT BRANCH,INTRAMURAL RES PROGRAM BETHESDA MD 20892
Titolo Testata:
The Journal of neuroscience
fascicolo: 1, volume: 18, anno: 1998,
pagine: 419 - 427
SICI:
0270-6474(1998)18:1<419:BDNIBT>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
COCAINE BINDING-SITES; TYROSINE-HYDROXYLASE ACTIVITY; NOREPINEPHRINE UPTAKE SITES; LESCH-NYHAN DISEASE; PARKINSONS-DISEASE; STRIATAL DOPAMINE; RAT-BRAIN; NERVE-TERMINALS; SINGLE INJECTION; C-11 WIN-35,428;
Keywords:
METHAMPHETAMINE; DOPAMINE; NEUROTOXICITY; PET; PRIMATES; WIN-35,428;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
74
Recensione:
Indirizzi per estratti:
Citazione:
V. Villemagne et al., "BRAIN DOPAMINE NEUROTOXICITY IN BABOONS TREATED WITH DOSES OF METHAMPHETAMINE COMPARABLE TO THOSE RECREATIONALLY ABUSED BY HUMANS - EVIDENCE FROM [C-11] WIN-35,428 POSITRON-EMISSION-TOMOGRAPHY STUDIES AND DIRECT IN-VITRO DETERMINATIONS", The Journal of neuroscience, 18(1), 1998, pp. 419-427

Abstract

The present study sought to determine whether doses of methamphetamine in the range of those used recreationally by humans produce brain dopamine (DA) neurotoxicity in baboons and to ascertain whether positronemission tomography (PET) imaging with the DA transporter (DAT) ligand [C-11]WIN-35,428 ([C-11]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)-tropane) could be used to detect methamphetamine-induced DAT loss in living primates. Baboons were treated with saline (n = 3) or one of three doses of methamphetamine [0.5 mg/kg (n = 2); 1 mg/kg (n = 2); and 2mg/kg (n = 3)], each of which was given intramuscularly four times at2 hr intervals. PET studies were performed before and 2-3 weeks aftermethamphetamine treatment. After the final PET studies, animals were killed for direct neurochemical determination of brain DA axonal markers. PET-derived binding potential values, used to index striatal DAT density, were significantly decreased after methamphetamine, with larger decreases occurring after higher methamphetamine doses. Reductions in striatal DAT documented by PET were associated with decreases in DA,dihydroxyphenylacetic acid, and specific [H-3]WIN-35,428 and [H-3]DTBZ binding determined in vitro. Decreases in DAT detected with PET werehighly correlated with decreases in specific [H-3]WIN-35,428 binding determined in vitro in the caudate of the same animal (r = 0.77; p = 0.042). These results indicate that methamphetamine, at doses used by some humans, produces long-term reductions in brain DA axonal markers in baboons, and that it is possible to detect methamphetamine-induced DAT loss in living nonhuman primates by means of PET.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 00:40:32