Alteration of neuroinflammation detected by 18F-GE180 PET imaging in place-conditioned rats with morphine withdrawal

Abstract

Background Accumulating evidence indicates that neuroinflammation (NI) significantly contributes to drug addiction, but the conversion of NI after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of NI during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180. Methods Twelve male adult Sprague–Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A 18F-GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t test using SPM8. Results Both the DW group and the CPA group spent less time in the conditioning cage during the post-test phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. − 159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group. Conclusion In morphine-dependent rats, Neuroinflammation (NI) became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this NI induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.

Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell‐derived secretome in preclinical models of morphine dependence

“…This evaluation holds particular relevance in light of evidence indicating the occurrence of hippocampal neuroinflammation caused by naloxone administration in a morphine dependence rat model. 67 As expected, rats that received morphine exhibited a significant increase in astrocyte density compared to control rats (p < 0.01, One-way ANOVA followed by Tukey's post-hoc test) (Figure 3A,C). A similar trend was observed for microglial density.…”

“…Considering the pivotal role of the hippocampus in associative memory networks, the encoding and consolidation of novel environmental information, and its documented contribution to the development of drug‐seeking memory behavior, 65,66 we evaluated neuroinflammation in this brain region in the morphine antagonist‐triggered withdrawal model prior to naloxone administration. This evaluation holds particular relevance in light of evidence indicating the occurrence of hippocampal neuroinflammation caused by naloxone administration in a morphine dependence rat model 67 . As expected, rats that received morphine exhibited a significant increase in astrocyte density compared to control rats ( p < 0.01, One‐way ANOVA followed by Tukey's post‐hoc test) (Figure 3A,C).…”

Brain glucose metabolism and dopamine transporter changes in rats with morphine‐induced conditioned place preference

“…Micro‐PET/CT imaging in these rats was conducted at designed time points in accordance with a previously described method 26,30,31 . Briefly, the rats were anaesthetized with 2% isoflurane in 100% oxygen (1 L/min) at room temperature using an isoflurane vaporizer (Molecular Imaging Products Company, USA).…”

“…Micro-PET/CT imaging in these rats was conducted at designed time points in accordance with a previously described method. 26,30,31 Briefly, the rats were anaesthetized with 2% isoflurane in 100% oxygen (1 L/min) at room temperature using an isoflurane vaporizer (Molecular Imaging Products Company, USA). The rats were positioned in a spread-supine position on the imaging bed and subjected to 2% isoflurane in 100% oxygen (1 L/min) via inhalation during the PET/CT procedure.…”