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: Experiment 1 determined if prenatal folate modulated the effects of PEE on ethanol intake, anxiety-like response, and exploratory behaviors (Experiment 1) in Wistar rats. 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 vehicle only 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 (η² ps = 0.06–07) and induced hyperactivity and a reduced latency to exit the white area of the LDB (η² ps = 0.12–17). These effects were partially inhibited by folate (p > .05). Rats exposed to ethanol exposure at adolescence exhibited reduced motor activity (η² p = .17), regardless of 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.

KEYWORDS:

• Prenatal ethanol exposure
• folate
• intermittent ethanol
• adolescent rats
• anxiety

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributors

Conceptualization, Visualization, Writing, Original draft preparation: Leonardo Marengo, Iván Servín Bernal, Agustín Salguero, Ignacio Morón, Cruz Miguel Cendán, Ricardo Pautassi. Funding acquisition: Ricardo Pautassi, Juan Carlos Molina, Claudio D’Addario, María Carolina Fabio. Data curation, Project administration, Investigation: Leonardo Marengo, María Carolina Fabio, Agustín Salguero, Ricardo Pautassi, Iván Servín Bernal, María Carolina Fabio. Project administration, Resources: Leandro Ruiz Leyva, Agustín Salguero. Writing, Original draft preparation, Resources: Juan Carlos Molina, Claudio D’Addario.

Supplementary matrial

Supplemental data for this article can be accessed online at https://10.1080/00952990.2022.2159425.

Additional information

Funding

This work was supported by PICT-2019- 00180 and PICT-2018-00597 of FONCyT-Argentina to RMP. The funder had no further role in study design, in the collection, analysis, and interpretation of data, in the writing of the report and in the decision to submit the paper for publication.