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

Abstract

We verified if cocaine-induced peripheral activation might disrupt [ 18 F]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 [ 18 F]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [ 18 F]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 [ 18 F]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. [ 18 F]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 [ 18 F]FDG PET, providing an interesting preclinical approach to investigate naïve subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder.

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

“…As we previously showed, acute and repeated cocaine administration was also associated with higher glucose metabolism (Spelta et al., 2022). However, considering the whole brain and the hippocampus, 8 days of CBD administration prevented the increase in glucose metabolism after the challenge with cocaine.…”

“…Considering the effects of cocaine at the challenge, no differences were seen when compared to the baseline and the effect size of this comparison was moderate ( d = .63, 95% CI .33–1.53). In a previous study, we showed that an acute cocaine injection induces a significant increase in glucose metabolism (Spelta et al., 2022). On the other hand, our results here suggest that CBD was able to attenuate the metabolism increase promoted by cocaine.…”

“…After 3 days, animals received cocaine (20 mg/kg, i.p.) or saline .9%, every other day for 9 days (days 4–12; a total of five administrations), in a behavior sensitization protocol (Spelta et al., 2022). During the sensitization phase, in the first four administrations, the mice were exposed to the open field (a circular arena of 40 × 40 cm) for 30 min immediately after cocaine or saline administration.…”

“…PET images were acquired in a small‐animal PET scanner (Triumph Trimodality, Gamma Medica‐Ideas Inc., California, US), using the experimental protocol established by Spelta et al. (2022).…”

“…Using [ 18 F]FDG PET, our study group has previously shown that both acute and repeated cocaine administration (five administrations every other day) lead to a global increase in brain metabolic activity (Spelta et al., 2022). However, there is currently a lack of small animal [ 18 F]FDG PET data investigating the effects of CBD, in CUD models in small animals.…”