[18F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study

We verified if cocaine-induced peripheral activation might disrupt [F-18]FDG brain uptake after a cocaine challenge and suggested an optimal protocol to measure cocaine-induced brain metabolic alterations in mice. C57Bl/6 male mice were injected with [F-18]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [F-18]FDG administration and after 5 min received saline or cocaine (20 mg/kg). The animals in group 1 (n = 5) were then evaluated in the open field for 30 min and those from group 2 (n = 6) were kept alone in a home cage for the same period. Forty-five minutes after [F-18]FDG administration, images were acquired for 30 min. Group 3 (n = 6) was kept anesthetized and image acquisition started immediately after tracer injection, for 75 min. Saline (Day 1) or cocaine (Day 2) was injected 5 min after starting acquisition. Another set of animals (n = 5) were treated with cocaine every other day for 10 days or saline (n = 6) and were scanned with the dynamic protocol to verify its efficacy. [F-18]FDG uptake increased after cocaine administration when compared to baseline only in animals kept under anesthesia. No brain effect of cocaine was observed in animals submitted to the open field or kept in the home cage. The use of anesthesia is essential to visualize cocaine-induced changes in brain metabolism by [F-18]FDG PET, providing an interesting preclinical approach to investigate naive subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder.

Automated summary

We investigated the effects of cocaine-induced peripheral activation on brain [F-18]FDG uptake and proposed an optimal protocol for measuring cocaine-induced brain metabolic alterations in mice. Our findings suggest that anesthesia is essential for visualizing cocaine-induced changes in brain metabolism using [F-18]FDG PET, providing a valuable preclinical approach for studying cocaine use disorder.