Methamphetamine increases basal ganglia iron to levels observed in aging.
Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.
Melega
William P
WP
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, California, USA. wmelega@mednet.ucla.edu
Laćan
Goran
G
Harvey
Dennis C
DC
Way
Baldwin M
BM
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000633:toxicity; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005293:Ferritins / Q000187:drug effects / Q000378:metabolism; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D005293:Ferritins; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine