Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity.

Abstract	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 alpha1b-adrenergic receptors (ARs). MA-stimulated striatal DA release (measured by microdialysis in freely moving animals) and locomotor activity were also reduced in alpha1b-AR knockout mice. Pharmacological blockade of alpha-adrenergic receptors with prazosin also protected wild-type mice against MA toxicity. These results suggests that alpha1b-ARs may play a role in the toxicity of MA on nigro-striatal DA neurons.
Authors	Giuseppe Battaglia, Francesco Fornai, Carla Letizia Busceti, Giuseppe Lembo, Ferdinando Nicoletti, Antonio De Blasi
Journal	Journal of neurochemistry (J Neurochem) Vol. 86 Issue 2 Pg. 413-21 (Jul 2003) ISSN: 0022-3042 [Print] England
PMID	12871582 (Publication Type: Journal Article)
Chemical References	ADRA1B protein, human Adra1b protein, mouse Adrenergic alpha-1 Receptor Antagonists Adrenergic alpha-Antagonists Central Nervous System Stimulants Dopamine Plasma Membrane Transport Proteins Membrane Glycoproteins Membrane Transport Proteins Nerve Tissue Proteins Receptors, Adrenergic, alpha-1 3,4-Dihydroxyphenylacetic Acid Methamphetamine 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Tyrosine 3-Monooxygenase Dopamine Homovanillic Acid Prazosin
Topics	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology) 3,4-Dihydroxyphenylacetic Acid (analysis, metabolism) Adrenergic alpha-1 Receptor Antagonists Adrenergic alpha-Antagonists (pharmacology) Animals Behavior, Animal (drug effects) Body Temperature (drug effects) Central Nervous System Stimulants (toxicity) Corpus Striatum (drug effects, metabolism, pathology) Cytoprotection (drug effects, genetics) Dopamine (analysis, metabolism) Dopamine Plasma Membrane Transport Proteins Gliosis (chemically induced, pathology) Homovanillic Acid (analysis, metabolism) MPTP Poisoning (chemically induced, drug therapy) Male Membrane Glycoproteins Membrane Transport Proteins (metabolism) Methamphetamine (toxicity) Mice Mice, Knockout Microdialysis Motor Activity (drug effects) Nerve Tissue Proteins Prazosin (pharmacology) Receptors, Adrenergic, alpha-1 (deficiency, genetics) Tyrosine 3-Monooxygenase (metabolism)

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