Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats

Abstract

Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety.

Effects of sex and housing on social, spatial, and motor behavior in adult rats exposed to moderate levels of alcohol during prenatal development

“…Thus, females are not generally immune to the behavioral and cognitive effects of moderate PAE, however, considered with the present findings, the effects of moderate PAE on social behavior and other behaviors that depend upon ventrolateral frontal cortex appear to be considerably greater in males. We note that several other studies have also reported sexually dimorphic effects of developmental alcohol exposure on social behavior [12, 14, 29, 52, 75], several of which have reported more pronounced effects in males compared to relatively lower, opposing, or absent effects in females. Those studies have typically employed higher levels of ethanol than used here (e.g., > 125 mg/dl) and recent evidence indicates that low levels of ethanol exposure during gestation (~30mg/dl) alters social investigation in males but not females [12].…”

Ifenprodil infusion in agranular insular cortex alters social behavior and vocalizations in rats exposed to moderate levels of ethanol during prenatal development

“…All post hoc analyses used a Bonferroni correction (adjusted p < 0.025) to correct for the number of multiple comparisons. Due to the fact that there were a number of Sex effects on behavior observed in this study, earlier studies from our laboratory [39, 40, 53], and the work of others [38, 43, 67, 68], we also present the effects of Prenatal Treatment and Drug Treatment on behavior separately by level of sex.…”

Increased Ethanol Intake is Associated with Social Anxiety in Offspring Exposed to Ethanol on Gestational Day 12

“…Consistent with neurobehavioral deficits associated with FASD, animal models have recapitulated many of the long-lasting effects of PAE. For example, many groups have shown that PAE across various gestational periods can alter non-social anxiety-like behaviors at various ages [15-27]. In rodents, PAE also leads to increased ethanol intake in offspring across various ages [28-35].…”

“…Alterations in social behavior have also been observed in rodents exposed to ethanol in utero [36-43]. Importantly, we have shown that a single exposure to a high dose of ethanol on gestational day (G) 12 increases social anxiety-like behaviors in an age- and sex-dependent manner in two strains of rats, Long Evans [44] and Sprague Dawley [27]. Additionally, G12 exposed adolescent offspring exhibited reduced sensitivity to the socially anxiogenic effects of an acute ethanol challenge, and demonstrated social facilitation at low-doses of ethanol known to not alter social behavior in control rats [45].…”