1. ¹Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, The Asher Center, Chicago, IL, USA
2. ²Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Correspondence: Dr EE Redei, PhD, The Asher Center, Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Ward 9-198, Chicago, IL 60611, USA. E-mail: e-redei@northwestern.edu

Received 5 January 2005; Revised 12 April 2005; Accepted 27 April 2005; Published online 31 May 2005.

Abstract

Children prenatally exposed to alcohol typically exhibit behavioral abnormalities, including hyperactivity, learning deficits, and an increased prevalence of depression. Similar impairments are found in children of hypothyroid mothers, and we have shown that alcohol-consuming rat dams have suppressed hypothalamic–pituitary–thyroid (HPT) function. Therefore, we hypothesized that suppressed maternal thyroid hormonal milieu may contribute to the deleterious consequences of prenatal alcohol exposure. We aimed first to confirm and then to reverse the behavioral deficits in the fetal alcohol exposed (FAE) rat offspring by administration of thyroxine (T4) to the alcohol-consuming dams. Adult offspring prenatally exposed to ethanol (FAE; 35% ethanol-derived calories), pair-fed (PF) or control (C) diets were tested in the Morris water maze (MWM), the forced swim test (FST), and the open field test (OFT) to assess spatial learning, depressive behavior, and exploratory behavior/anxiety, respectively. Adult FAE offspring took longer to locate a hidden platform in the MWM and showed increased depressive behavior in the FST both of which were reversed by administration of T4 to the alcohol-consuming mother. We found sex and brain region-specific alterations in expression of genes involved in these behaviors in FAE adult offspring. Specifically, decreased hippocampal GAP-43 mRNA levels in adult FAE females and decreased glucocorticoid receptor (GR) expression in the amygdala of male and female FAE offspring were observed. The decreased mRNA levels of GAP-43 and GR were normalized by T4 treatment to the alcohol-consuming mother. Our results suggest that the suppressed HPT function of the alcohol-consuming mother contributes to the behavioral and cognitive dysfunctions observed in the offspring.