Folate administration ameliorates neurobehavioral effects of prenatal ethanol exposure

Abstract

Background: Prenatal ethanol exposure (PEE) induces heightened ethanol intake at adolescence in preclinical studies. Ethanol intake alters the absorption of folate, a methyl-group donor critical for numerous cellular functions. The prenatal administration of folate is, therefore, a promising approach to reduce the effects of PEE. Objectives: We tested, in Wistar rats, if prenatal folate modulated the effects of PEE on ethanol intake, anxiety-like response, and exploratory behaviors (Experiment 1). Experiment 2 assessed, in rats not given PEE, if postnatal folate reversed effects of ethanol exposure at postnatal days 28-42. Experiment 3 assessed if folate altered blood ethanol levels (BELs). Methods: Experiment 1 involved 242 (125 male) adolescent Wistar rats derived from dams given folate (20 mg/kg, gestational days ?GD- 13-20) + ethanol (2.0 g/kg, GD 17-20), ethanol or only vehicle at pregnancy. Experiment 2 involved 29 male adolescents administered vehicle or ethanol doses co-administered or not with folate. In Experiment 3 twelve adult females were tested for BELs after folate administration. These tests were applied: intake tests, light dark box (LDB), elevated plus maze, open field and concentric square field. Results: PEE heightened ethanol intake (η²ps=0.06-07), and induced hyperactivity and a reduced latency to exit the white area of the LDB (η²ps=0.12-17). These effects were partially inhibited by folate (p>0.05). Rats exposed to ethanol exposure at adolescence exhibited reduced motor activity (η²p=0.17), regardless folate treatment. Folate did not affect BELs. Conclusion: Folate administration should be considered as a preventive or acute treatment to attenuate the neurobehavioral effects of PEE.