The first two authors contributed equally to this work.
Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity
Version of Record online: 4 FEB 2004
Journal of Neurochemistry
Volume 86, Issue 2, pages 413–421, July 2003
How to Cite
Battaglia, G., Fornai, F., Busceti, C. L., Lembo, G., Nicoletti, F. and De Blasi, A. (2003), Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity. Journal of Neurochemistry, 86: 413–421. doi: 10.1046/j.1471-4159.2003.01867.x
- Issue online: 4 FEB 2004
- Version of Record online: 4 FEB 2004
- Received November 22, 2002; revised manuscript received April 4, 2003; accepted April 4, 2003.
- α1-adrenergic receptor antagonists;
- methamphetamine neurotoxicity;
- Parkinson's disease
The psychostimulant methamphetamine (MA) is toxic to nigro-striatal 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.