Brain Glucose Metabolism and Dopamine Transporters Change in Addiction and Environmental Cue-Induced Memory

Abstract

Purpose: Drug addiction is a chronic brain disease and abuse of morphine is compulsive. Serval brain regions were involved in drug stimulus learning and drug seeking behaviors. Dopaminergic signaling pathway plays a key role in drug seeking behaviors. In this study, we focus on the regions of brain metabolism and dopamine transporters alternation, and figure out their role in drug seeking behaviors, and environmental cue-induced craving and retrieval of drug withdrawal memory by morphine-induced conditioned place preference (CPP) rats.Methods: Rats with CPP training (n = 6) were established by intraperitoneal injection of morphine (6 mg/kg body weight) in male SD rats (250 - 300g) during three-day conditioning, and rats with only morphine injection were used as addictive group (n = 6). Micro-PET/CT scans were performed at 3 different time points by intravenous injection of 18F-FDG and 11C-CFT. Regions of interests were collected by PMOD, voxel-wise analysis were performed by SPM8 software (uncorrected, P < 0.001, k = 20) on MATLAB platform. Results: SUVr of FDG declined significantly in medial prefrontal cortex (mPFC), cingulate in short term addiction compared with baseline. Glucose metabolism alternation in somatosensory cortex, hippocampus, cingulate were also found in addictive rats by voxel-wise analysis. Striatum, thalamus, medial prefrontal cortex, primary motor cortex and many regions in cortex also involved in CPP rats. Striatum, primary somatosensory cortex and some cortical regions play key roles in memory retrieval of addiction compared with addiction. DAT expression alternation were only observed in long term addiction compared with short term addiction.Conclusion: This study shows that the cerebral glucose metabolism in addiction and CPP is significantly different from control group mainly in mPFC, striatum and hippocampus. Hippocampal and neocortical circuits for episodic memories could also involve in memory retrieval of addiction, and primary somatosensory cortex, primary motor cortex could be the neocortical structure together with PFC.