Acute prenatal exposure to ethanol and social behavior: effects of age, sex, and timing of exposure

Abstract

During development of the central nervous system, neurons pass through critical periods of vulnerability to environmental factors. Exposure to ethanol during gastrulation or during neuronal generation results in a permanent reduction in the number of neurons in trigeminal-associated cranial nerve nuclei. Normal functioning of the trigeminal system is required for social behavior, the present study examined the effects of acute prenatal exposure to ethanol on social interactions across ontogeny. Pregnant Long-Evans rats were injected with 2.9 g/kg ethanol (i.p., 20%, v/v solution; peak blood ethanol concentrations of ∼300 mg/dl) or an equivalent volume of saline on gestational day (G) 7 (gastrulation) or G12 (neuronal generation). Subsequently, social investigation, play fighting, contact behavior, social motivation, and overall locomotor activity in the social context were assessed in male and female off-spring during early adolescence, late adolescence, or adulthood, on postnatal day (P) 28, P42, or P75, respectively, using a modified social interaction test. Ethanol exposure on G7 resulted in mild changes of social behavior evident in young adolescents only. In contrast, animals exposed to ethanol on G12 demonstrated pronounced behavioral deficits throughout ontogeny, with deficits being most robust in male off-spring. Males exposed to ethanol on G12 showed decreases in social investigation, contact behavior, and play fighting, whereas a decrease in social motivation, i.e., transformation of social preference into social avoidance, was evident at P42 and P75 regardless of sex. These findings show that acute exposure to ethanol alters social behavior, and that the timing of the exposure defines the behavioral outcome.

Figure 1

Effects of exposure to ethanol on G7 or G12 on social investigation of male and female rats tested as early adolescents (P28), late adolescents (P42) or adults (P75). Social investigation was defined as sniffing of any part of the body of the partner. Exposure to ethanol on G7 increased social investigation in young adolescent animals. In contrast, ethanol exposure on G12 decreased social investigation in male off-spring at all ages examined. An * depicts significant (p < 0.05) differences between age-matched saline- and ethanol-exposed animals. Bars show the mean for each group, t-bars depict the standard error of the mean.

Figure 2

Effects of exposure to ethanol on G7 or G12 on contact behavior of male and female rats tested as early adolescents (P28), late adolescents (P42) or adults (P75). Contact behavior was defined as social grooming and crawling over or under the partner. It was unaffected by ethanol exposure on G7 (top) but was significantly decreased at all ages in males exposed to ethanol on G12 (bottom). Notations as in Figure 1.

Figure 3

Effects of exposure to ethanol on G7 or G12 on play fighting as early adolescents (P28), late adolescents (P42) or adults (P75). Play fighting was defined as a sum of pouncing, chasing, and pinning. Play fighting was not altered by exposure to ethanol on G7. Ethanol exposure on G12 significantly (p<0.05) decreased play fighting in males at all ages examined. Notations as in Figure 1.

Figure 4

Effects of exposure to ethanol on social motivation. Movements of test animals towards or away from the novel animal were scored. Coefficient (%) = (crossovers to − crossovers from)/(crossovers to + crossovers from). No sex-effect was apparent for treatment on G7 or G12. Animals treated on G7 showed social preference at all ages, defined as positive values for the coefficient (top). Older adolescent and adult animals exposed to ethanol on G12 (bottom) showed social avoidance (indexed by negative values for the coefficient). Notations as in Figure 1.

Figure 5

Effects of exposure to ethanol on locomotor activity. Analysis of the total number of crossovers between the two compartments of the apparatus was used as an index of overall locomotor activity in the social context. Activity was higher in young adolescent animals treated with ethanol on G7 than in the age-matched saline-treated control animals (top). Prenatal treatment on G12 had no effect on locomotor activity (bottom). No sex effects were apparent for either treatment. Notations as in Figure 1.