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Titolo:
Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in mice
Autore:
Ali, SF; Haung, P; Itzhak, Y;
Indirizzi:
US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA US FDA Jefferson AR USA 72079 , Div Neurotoxicol, Jefferson, AR 72079 USA Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charleston, MA USA Massachusetts Gen Hosp Charleston MA USA asc Res Ctr, Charleston, MA USA Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA Univ Miami Miami FL USA ch Med, Dept Psychiat & Behav Sci, Miami, FL USA
Titolo Testata:
ADDICTION BIOLOGY
fascicolo: 3, volume: 5, anno: 2000,
pagine: 331 - 341
SICI:
1355-6215(200007)5:3<331:ROPIMD>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; INDUCED BEHAVIORAL SENSITIZATION; HEAT-SHOCK-PROTEIN; SEROTONERGIC NEUROTOXICITY; ENVIRONMENTAL-TEMPERATURE; PHARMACOLOGICAL AGENTS; INDUCED HYPERTHERMIA; LIPID-PEROXIDATION; STRIATAL DOPAMINE; DEFICIENT MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Ali, SF US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA US FDA HFT-132 Jefferson AR USA 72079 132, Jefferson, AR 72079 USA
Citazione:
S.F. Ali et al., "Role of peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity and sensitization in mice", ADDICT BIOL, 5(3), 2000, pp. 331-341

Abstract

Methamphetamine (METH)-induced dopaminergic neurotoxicity is thought to beassociated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recently, we have reported that copper/zinc(CuZn)-superoxide dismutase transgenic mice are resistant to METH-induced neurotoxicity. In the present study, we examined the role of the neuronal nitric oxide synthase (nNOS), susceptibility of nNOS knockout (KO) mice and sensitization to psychostimulants after neurotoxic doses of METH. Male Swiss Webster mice were treated with or without 7-nitroindazole (7-NI) along with METH (5 mg/kg,ip,q 3 h x 3) and were sacrificed 72 h after the last METH injection. Dopamine (DA) and dopamine transporter (DAT) binding sites were determined in striatum from saline and METH-treated animals. 7-NI completely protected against the depletion of DA, and DAT in striatum. In follow-up experiments nNOS KO mice along with appropriate control (C57BL/6N, SV129 and B6FSV129) mice were treated with METH (5 mg/kg,ip, q 3 h x 3) and were sacrificed 72 h after dosing. This schedule of METH administrations resulted in only 10-20% decrease in tissue content of DA and no apparent change in the number of DAT binding sites in nNOS KO mice. However, this regime of METH resulted in a significant decrease in the content of DA as well as DAT bindingsires in the wild-type animals. Pre-exposure to single or multiple doses of METH resulted in a marked locomotion sensitization in response to METH. However, the nNOS KO mice show no sensitization in response to METH after single or multiple injections of METH. Therefore, these studies strongly suggest the role of peroxynitrite, nNOS and DA system in METH-induced neurotoxicity and behavioral sensitization.

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Documento generato il 19/01/20 alle ore 10:03:15