title: Cocaine abuse in humans is not associated with increased microglial activation: an 18-kDa translocator protein positron emission tomography imaging study with [11C]PBR28.
abstract: Basic science investigations have consistently shown that repeated exposure to psychostimulant drugs, such as cocaine, activate the immune response and lead to inflammatory changes in the brain. No previous in vivo studies have confirmed this observation in chronic cocaine-abusing humans. To test this hypothesis, we used positron emission tomography imaging to measure the binding of [(11)C]PBR28 to the 18 kDa translocator protein (TSPO), a marker for microglial activation in a group of 15 recently abstinent cocaine abusers and 17 matched healthy controls. [(11)C]PBR28 volumes of distribution expressed relative to total plasma ligand concentration (VT) were measured in subjects with kinetic analysis using the arterial input function. Subjects were also genotyped for the TSPO alanine147 threonine (Ala147Thr, rs6971) polymorphism that has been shown to influence the in vivo binding of PBR28 to TSPO. Consistent with previous reports, the TSPO Ala147Thr genotype predicted the in vivo binding of [(11)C]PBR28. No significant differences in [(11)C]PBR28 VT were observed in the cortical and subcortical regions in cocaine abusers compared with healthy controls. The results of this in vivo study do not support increased TSPO expression and, by extension, microglial activation in chronic cocaine-abusing humans. Further research with more direct markers of microglial activation is necessary to conclusively rule out neuroinflammation in cocaine dependence.
authors: Departments of Radiology, Psychiatry, and narendranr@upmc.edu.
authors: Rajesh
authors: R
authors: Narendran
authors: Departments of Radiology.
authors: Brian J
authors: BJ
authors: Lopresti
authors: Departments of Radiology.
authors: Neale Scott
authors: NS
authors: Mason
authors: Departments of Radiology.
authors: Lora
authors: L
authors: Deuitch
authors: Psychiatry, and.
authors: Jennifer
authors: J
authors: Paris
authors: Psychiatry, and.
authors: Michael L
authors: ML
authors: Himes
authors: Psychiatry, and.
authors: Chowdari V
authors: CV
authors: Kodavali
authors: Psychiatry, and Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15213.
authors: Vishwajit L
authors: VL
authors: Nimgaonkar
mesh_terms: D000081:Acetamides / Q000378:metabolism*; D000328:Adult; D002250:Carbon Radioisotopes; D019970:Cocaine-Related Disorders / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D011725:Pyridines / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: PET; TSPO; [11C]PBR28; cocaine dependence; inflammation