The peroxisome proliferator-activated receptor alpha agonist fenofibrate attenuates alcohol self-administration in rats

- Fenofibrate reduced self-administration of EtOH under two reinforcement schedules.
- The effects of fenofibrate on EtOH self-administration were dose-dependent.
- The effects of fenofibrate on sucrose self-administration were not dose-dependent.
- First study to test fenofibrate on operant oral EtOH self-administration in rats.

Fibrates are a class of medications used to treat hypercholesterolemia and dyslipidemia that target nuclear peroxisome proliferator-activated receptors (PPARs). Studies have shown the PPARα agonist fenofibrate decreases voluntary EtOH consumption however its impact on the reinforcing and motivational effects of EtOH is unknown. We evaluated the ability of fenofibrate (25, 50 and 100 mg/kg), to alter EtOH (10%, w/v) and sucrose (2%, w/v) operant self-administration in rats under a FR2 schedule of reinforcement over four days and under a progressive ratio (PR) schedule on day five of treatment. Results showed fenofibrate dose-dependently decreased EtOH self-administration under both schedules of reinforcement with the greatest effects seen after four to five days of treatment. Fenofibrate decreased responding for sucrose only under the PR schedule of reinforcement and this effect was not dose-dependent. These findings provide further evidence for fenofibrate as a potential treatment for alcohol use disorder in humans.