Patterns of social-experience-related c-fos and Arc expression in the frontal cortices of rats exposed to saccharin or moderate levels of ethanol during prenatal brain development.

Recent findings from our laboratory indicate that alterations in frontal cortex function, structural plasticity, and related social behaviors are persistent consequences of exposure to moderate levels of ethanol during prenatal brain development [24]. Fetal-ethanol-related reductions in the expression of the immediate early genes (IEGs) c-fos and Arc and alterations in dendritic spine density in ventrolateral and medial aspects of frontal cortex suggest a dissociation reminiscent of that described by Kolb et al. [38] in which these aspects of frontal cortex undergo reciprocal experience-dependent changes. In addition to providing a brief review of the available data on social behavior and frontal cortex function in fetal-ethanol-exposed rats, the present paper presents novel data on social-experience-related IEG expression in four regions of frontal cortex (Zilles LO, VLO, Fr1, Fr2) that are evaluated alongside our prior data from AID and Cg3. Social experience in normal rats was related to a distinct pattern of IEG expression in ventrolateral and medial aspects of frontal cortex, with generally greater expression observed in ventrolateral frontal cortex. In contrast, weaker expression was observed in all aspects of frontal cortex in ethanol-exposed rats, with the exception of an experience-related increase in the medial agranular cortex. Behaviors related to social investigation and wrestling/boxing were differentially correlated with patterns of activity-related IEG expression in the regions under investigation for saccharin- and ethanol-exposed rats. These observations suggest that recruitment and expression of IEGs in frontal cortex following social experience are potentially important for understanding the long-term consequences of moderate prenatal ethanol exposure on frontal cortex function, synaptic plasticity, and related behaviors.