Tarbiat Modares University Pathobiology Research 2538-3000 29 2 2026 06 01 Effect of fenofibrate on the acquisition and reinstatement of ethanol-induced conditioned place preference in mice 35 42 28723 10.48311/mjms.2026.120351.82625 EN KOBRA SHIRANI Unit 6.No 1,North golestan Mahestan shahrak gharb Faezeh Vahdati Hassani Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Maliheh Ezati Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Ali Roohbakhsh Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Gholamreza Karimi Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Journal Article 2026 05 09 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.<br>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.<br>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).<br>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. https://mjms.modares.ac.ir/article_28723_d1dd537846e529e1101d7c23e170fe4b.pdf