Exploring the neuromechanism of chronic ephedrine addiction in rhesus monkeys: A behavioural and brain resting-state fMRI study

Abstract

Ephedrine is thought to exert behavioural effects primarily through actions on the central nervous system. However, the neuromechanism underlying the effects of ephedrine addiction still remains unclear. Our study aimed to establish chronic ephedrine addiction models in rhesus monkeys and to investigate the neuromechanism of chronic ephedrine addiction using the behavioural methods combined with resting-state blood oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI). Monkeys in the ephedrine addiction group (n = 6) received intramuscular injections of ephedrine using a dose escalation method, with a chronic model established in 8 weeks, while in the control group (n = 4), monkeys received a pure 0.9% saline injection. The weight and behaviors of the monkeys were observed throughout the treatment. All monkeys underwent the brain MR scans for two times (before treatment and after treatment had been discontinued). After molding, the weight of the ephedrine group was significantly reduced, while the weight of the control group increased significantly. Compared with the control group, the ephedrine addicted monkeys showed more abnormal behaviors related to addiction. In fMRI study, the ephedrine addicted monkeys showed more increased brain activation than that of the control group, mainly including the prefrontal cortex(PFC) and anterior cingulate cortex (ACC), the left ventral tegmental area(VTA), right insula, right amygdala, hippocampus, left thalamus, and left cerebellum.We hypothesize that the principal neuromechanism underlying chronic ephedrine addiction involves multiple abnormal brain neuron circuits, mainly in the PFC and the limbic system, and is closely related to addictive behaviors.