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Evaluation of TSPO PET imaging, a marker of glial activation, to study the neuroimmune footprints of morphine exposure and withdrawal.

Abstract：

INTRODUCTION:A growing area of research suggests that neuroimmunity may impact the pharmacology of opioids. Microglia is a key component of the brain immunity. Preclinical and clinical studies have demonstrated that microglial modulators may improve morphine-induced analgesia and prevent the development of tolerance and dependence. Positron emission tomography (PET) using translocator protein 18kDa (TSPO) radioligand is a clinically validated strategy for the non-invasive detection of microglial activation. We hypothesized that TSPO PET imaging may be used to study the neuroimmune component of opioid tolerance and withdrawal. METHODS:Healthy rats (n=6 in each group) received either saline or escalating doses of morphine (10-40mg/kg) on five days to achieve tolerance and a withdrawal syndrome after morphine discontinuation. MicroPET imaging with [18F]DPA-714 was performed 60h after morphine withdrawal. Kinetic modeling was performed to estimate [18F]DPA-714 volume of distribution (VT) in several brain regions using dynamic PET images and corresponding metabolite-corrected input functions. Immunohistochemistry (IHC) experiments on striatal brain slices were performed to assess the expression of glial markers (Iba1, GFAP and CD68) during 14days after morphine discontinuation. RESULTS:The baseline binding of [18F]DPA-714 to the brain (VT=0.086±0.009mLcm-3) was not increased by morphine exposure and withdrawal (VT=0.079±0.010mLcm-3) indicating the absence of TSPO overexpression, even at the regional level. Accordingly, expression of glial markers did not increase after morphine discontinuation. CONCLUSIONS:Morphine tolerance and withdrawal did not detectably activate microglia and had no impact on [18F]DPA-714 brain kinetics in vivo.

journal_name

Drug Alcohol Depend

journal_title

Drug and alcohol dependence

authors

Auvity S,Goutal S,Thézé B,Chaves C,Hosten B,Kuhnast B,Saba W,Boisgard R,Buvat I,Cisternino S,Tournier N

doi

10.1016/j.drugalcdep.2016.10.037

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

43-50

eissn

0376-8716

issn

1879-0046

pii

S0376-8716(16)30988-7

journal_volume

170

pub_type

杂志文章

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