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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Marche
Kévin
K
Département de Pharmacologie Médicale-Centre Hospitalier Universitaire, Université Lille-Nord-de-France-Faculté de Médecine, 1, Place de Verdun, 59-045, Lille Cedex, France. kevin.marche@live.fr
Danel
Thierry
T
Bordet
Régis
R
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy* / Q000503:physiopathology; D006948:Hyperkinesis / Q000209:etiology / Q000517:prevention & control*; D007774:Lactation; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D047493:PPAR alpha; D011345:Fenofibrate