Enhancement of fear learning in PPARα knockout mice

•PPARα knockout mice showed enhanced fear learning.•Dopamine and its metabolites were increased in the amygdala of PPARα knockout mice.•The mRNA expression of dopamine-degrading enzymes was decreased in the amygdala of PPARα knockout mice.•Injection of a dopamine D1 receptor antagonist attenuated the enhanced fear learning observed in PPARα knockout mice.•PPARα is responsible for controlling emotional memory via the dopamine pathway in the amygdala. Peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily and regulates fatty acid oxidation. Although PPARα is expressed not only in the peripheral tissues but also in the brain, its role in higher brain function is unclear. In this study, we investigated the role of PPARα in the control of behavior, including memory/learning and mood change, using PPARα knockout (KO) mice. A significant difference between wild-type (WT) and KO mice was seen in the passive avoidance test, demonstrating that KO mice showed enhanced fear leaning. In the amygdala of KO mice, the levels of dopamine and its metabolites were increased, and the mRNA expression of dopamine degrading enzyme was decreased. When dopamine D1 receptor antagonist was administered, the enhanced fear learning observed in KO mice was attenuated. These results suggest that PPARα is involved in the regulation of emotional memory via the dopamine pathway in the amygdala.