Chronic Methamphetamine Effects on Brain Structure and Function in Rats.
Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity.
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, United States of America.
Panayotis K
PK
Thanos
Department of Psychology, UNC Chapel Hill, Chapel Hill, NC, United States of America.
Ronald
R
Kim
Department of Pharmacology, School of Medicine, University of Ioannina, Ioannina, Greece.
Foteini
F
Delis
Department of Neuroscience, Stony Brook University, Stony Brook, NY, United States of America.
Mala
M
Ananth
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, United States of America.
George
G
Chachati
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, United States of America.
Mark J
MJ
Rocco
Department of Biomedical Systems and Informatics Engineering, Hijjawi Faculty for Engineering Technology, Yarmouk University, Irbid 21163, Jordan
Ihssan
I
Masad
National High Magnetic Field Laboratory, Tallahassee, FL, United States of America.
Jose A
JA
Muniz
National High Magnetic Field Laboratory, Tallahassee, FL, United States of America.
Samuel C
SC
Grant
Washington University School of Medicine, Department of Psychiatry, St. Louis, MO, United States of America.
Mark S
MS
Gold
Molecular Neuropsychiatry Research Branch, NIDA, NIH, Department of Health and Human Services, Baltimore, MD, United States of America.
Jean Lud
JL
Cadet
Laboratory of Neuroimaging, NIAAA, NIH, Department of Health and Human Services, Bethesda, MD, United States of America.
Nora D
ND
Volkow
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002908:Chronic Disease; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism
D019788:Fluorodeoxyglucose F18; D008694:Methamphetamine