Effect of fenofibrate on the acquisition and reinstatement of ethanol-induced conditioned place preference in mice

Introduction: Fenofibrate is a ligand for peroxisome proliferator-activated receptors (PPARs) and increases catalase activity in the liver. Hence, it could be a potential candidate to mitigate alcohol dependence. Here, we tested whether fenofibrate attenuates alcohol dependency in a mouse model.
Methods: Conditioned place preference (CPP) was induced in male mice. Three groups were used: 1. Saline-Ethanol / Saline-Saline; 2. Saline-Ethanol / Fenofibrate -Ethanol ; 3. Saline-Saline/ Fenofibrate -Saline. CPP was defined as significantly more time spent on the drug-paired floor (grid) versus the saline-paired floor (hole). After extinction, reinstatement was triggered by a priming dose of ethanol, with or without fenofibrate pretreatment.
Results: Ethanol (2 g/kg) significantly increased time spent on the grid floor compared to the hole floor (P < 0.01), indicating successful CPP. Fenofibrate alone did not induce CPP (P > 0.05). In the fenofibrate + ethanol group, no significant difference was observed between grid and hole times (P > 0.05), indicating inhibition of CPP acquisition. During extinction, place conditioning was absent in all groups. Pretreatment with fenofibrate significantly reduced reinstatement of ethanol-induced CPP (P < 0.05).
Conclusion: Fenofibrate reversed the establishment of ethanol-induced CPP and attenuated its reinstatement in mice. These findings suggest that fenofibrate may be a potential candidate for further research on alcohol dependence, though additional investigations are needed.