TY - JOUR
T1 - Alpha-1b adrenergic receptor knockout mice are protected against methamphetamine toxicity
AU - Battaglia, Giuseppe
AU - Fornai, Francesco
AU - Busceti, Carla Letizia
AU - Lembo, Giuseppe
AU - Nicoletti, Ferdinando
AU - De Blasi, Antonio
PY - 2003/7
Y1 - 2003/7
N2 - The psychostimulant methamphetamine (MA) is toxic to nigrostriatal dopaminergic terminals in both experimental animals and humans. In mice, three consecutive injections of MA (5 mg/kg, i.p. with 2 h of interval) induced a massive degeneration of the nigro-striatal pathway, as reflected by a 50% reduction in the striatal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC), by a substantial reduction in striatal tyrosine hydroxylase and high-affinity DA transporter immunostaining, and by the development of reactive gliosis. MA-induced nigro-striatal degeneration was largely attenuated in mice lacking α1b-adrenergic receptors (ARs). MA-stimulated striatal DA release (measured by microdialysis in freely moving animals) and locomotor activity were also reduced in α1b-AR knockout mice. Pharmacological blockade of α-adrenergic receptors with prazosin also protected wild-type mice against MA toxicity. These results suggests that α1b-ARs may play a role in the toxicity of MA on nigro-striatal DA neurons.
AB - The psychostimulant methamphetamine (MA) is toxic to nigrostriatal dopaminergic terminals in both experimental animals and humans. In mice, three consecutive injections of MA (5 mg/kg, i.p. with 2 h of interval) induced a massive degeneration of the nigro-striatal pathway, as reflected by a 50% reduction in the striatal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC), by a substantial reduction in striatal tyrosine hydroxylase and high-affinity DA transporter immunostaining, and by the development of reactive gliosis. MA-induced nigro-striatal degeneration was largely attenuated in mice lacking α1b-adrenergic receptors (ARs). MA-stimulated striatal DA release (measured by microdialysis in freely moving animals) and locomotor activity were also reduced in α1b-AR knockout mice. Pharmacological blockade of α-adrenergic receptors with prazosin also protected wild-type mice against MA toxicity. These results suggests that α1b-ARs may play a role in the toxicity of MA on nigro-striatal DA neurons.
KW - α1-adrenergic receptor antagonists
KW - Methamphetamine neurotoxicity
KW - Parkinson's disease
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U2 - 10.1046/j.1471-4159.2003.01867.x
DO - 10.1046/j.1471-4159.2003.01867.x
M3 - Article
C2 - 12871582
AN - SCOPUS:0037817358
VL - 86
SP - 413
EP - 421
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -