Fetal alcohol-induced hyperactivity is reversed by treatment with the PPARα agonist fenofibrate in a rat model

Exposure to alcohol in utero is linked to the development of a wide range of psychobehavioral changes, notably hyperactivity and attention deficit, with complex underlying pathological and functional mechanisms. Although the currently available treatments for hyperactivity have been studied in children exposed to alcohol in utero, the efficacy of these compounds is subject to debate and has prompted efforts to identify new pharmacological targets. In a rat model of early alcohol exposure (i.e., in utero and during lactation), we studied the effect of the lipid-lowering peroxisome proliferator-activated receptor (PPAR) alpha activator fenofibrate on psychobehavioral impairments. In the young rat, early exposure to alcohol perturbs locomotor behavior and induces prepubertal hyperactivity and postpubertal hypoactivity. The hyperactivity, usually observed at the end of the fifth week of life, was prevented by the administration of fenofibrate, which also had a beneficial effect on the accompanying attention deficit by reinforcing sustained attention. Our results with fenofibrate suggest that the pharmacological modulation of nuclear receptors such as PPAR-alpha may constitute a new therapeutic approach to managing the psychobehavioral disorders associated with early alcohol exposure.