Methamphetamine causes microglial activation in the brains of human abusers.
Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.
Sekine
Yoshimoto
Y
Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA.
Ouchi
Yasuomi
Y
Sugihara
Genichi
G
Takei
Nori
N
Yoshikawa
Etsuji
E
Nakamura
Kazuhiko
K
Iwata
Yasuhide
Y
Tsuchiya
Kenji J
KJ
Suda
Shiro
S
Suzuki
Katsuaki
K
Kawai
Masayoshi
M
Takebayashi
Kiyokazu
K
Yamamoto
Shigeyuki
S
Matsuzaki
Hideo
H
Ueki
Takatoshi
T
Mori
Norio
N
Gold
Mark S
MS
Cadet
Jean L
JL
D000328:Adult; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D017628:Microglia / Q000000981:diagnostic imaging / Q000187:drug effects*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects
D000970:Antineoplastic Agents; D002247:Carbon Isotopes; D000697:Central Nervous System Stimulants; D007546:Isoquinolines; D008694:Methamphetamine; C037850:PK 11195