Premium
Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F‐18]FEPPA
Author(s) -
Rathitharan Gausiha,
Truong Jennifer,
Tong Junchao,
McCluskey Tina,
Meyer Jeffrey H.,
Mizrahi Romina,
Warsh Jerry,
Rusjan Pablo,
Kennedy James L.,
Houle Sylvain,
Kish Stephen J.,
Boileau Isabelle
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12876
Subject(s) - translocator protein , radioligand , microglia , positron emission tomography , methamphetamine , binding potential , medicine , neuroscience , neuroimaging , pathology , psychology , receptor , inflammation
Activation of brain microglial cells, microgliosis, has been linked to methamphetamine (MA)–seeking behavior, suggesting that microglia could be a new therapeutic target for MA use disorder. Animal data show marked brain microglial activation following acute high‐dose MA, but microglial status in human MA users is uncertain, with one positron emission tomography (PET) investigation reporting massively and globally increased translocator protein 18 kDa (TSPO; [C‐11](R)‐PK11195) binding, a biomarker for microgliosis, in MA users. Our aim was to measure binding of a second‐generation TSPO radioligand, [F‐18]FEPPA, in brain of human chronic MA users. Regional total volume of distribution ( V T ) of [F‐18]FEPPA was estimated with a two‐tissue compartment model with arterial plasma input function for 10 regions of interest in 11 actively using MA users and 26 controls. A RM‐ANOVA corrected for TSPO rs6971 polymorphism was employed to test significance. There was no main effect of group on [F‐18]FEPPA V T ( P = .81). No significant correlations between [F‐18]FEPPA V T and MA use duration, weekly dosage, blood MA concentrations, regional brain volumes, and self‐reported craving were observed. Our preliminary findings, consistent with our earlier postmortem data, do not suggest substantial brain microgliosis in MA use disorder but do not rule out microglia as a therapeutic target in MA addiction. Absence of increased [F‐18]FEPPA TSPO binding might be related to insufficient MA dose or blunting of microglial response following repeated MA exposure, as suggested by some animal data.