Atypical Social Development in Vasopressin-Deficient Brattleboro Rats

Abstract

Over the past 3 decades, a large body of evidence has accumulated demonstrating that the neuropeptide arginine vasopressin (AVP) plays a critical role in regulating social behavior. The overwhelming majority of this evidence comes from adults, leaving a gap in our understanding of the role of AVP during development. Here, we investigated the effect of chronic AVP deficiency on a suite of juvenile social behaviors using Brattleboro rats, which lack AVP due to a mutation in the Avp gene. Social play behavior, huddling, social investigation & allogrooming, and ultrasonic vocalizations (USVs) of male and female rats homozygous for the Brattleboro mutation (Hom) were compared with their wild-type (WT) and heterozygous (Het) littermates during same-sex, same-genotype social interactions. Male and female Hom juveniles exhibited less social play than their Het and WT littermates throughout the rise, peak, and decline of the developmental profile of play. Hom juveniles also emitted fewer prosocial 50 kHz USVs, and spectrotemporal characteristics (call frequency and call duration) of individual call types differed from those of WT and Het juveniles. However, huddling behavior was increased in Hom juveniles, and social investigation and 22 kHz USVs did not differ across genotypes, demonstrating that not all social interactions were affected in the same manner. Collectively, these data suggest that the Avp gene plays a critical role in juvenile social development.

Keywords: play behavior; postnatal development; social behavior; ultrasonic vocalizations; vasopressin.

Figure 1.

Hom Brattleboro weanlings play less than their WT and Het littermates. A, B, Number of total play behaviors (A) and pins (B) of Hom, Het, and WT rats during a 20 min test at P17, P19, P21, or P23. Sample sizes are indicated within each bar. Data from each age were obtained from separate cohorts of animals. Genotypes with differing letters differ significantly from each other (p < 0.05, Fisher’s PLSD); where differences approach significance, the p value is included in parentheses next to the letter representing the appropriate comparison. See Results for ANOVA details.

Figure 2.

Social play is decreased in Hom Brattleboro juveniles. A, B, Number of pins (A) and play attacks (B) of male and female Hom, Het, and WT rats during a 20 min test at P34 or P44. C, D, The temporal profile of play is illustrated in C (for P34) and D (for P44) as the number of total play behaviors binned every 5 min. Sample sizes are indicated within each bar in A and B. Data from each age were obtained from separate cohorts of animals. Genotypes with differing letters differ significantly from each other (p < 0.05, Fisher’s PLSD); where differences approach significance, the p value is included in parentheses next to the letter representing the appropriate comparison. In C and D, significant differences between Hom and WT or Het rats within each bin are indicated by * and #, respectively (p < 0.005, Fisher’s PLSD). See Results for ANOVA details.

Figure 3.

Social behavior is altered in Hom Brattleboro juveniles. A–D, Number of total social behaviors (A), total play behaviors (B), social investigation & allogrooming behaviors (C), and huddling episodes (D) of Hom, Het, and WT rats during a 20 min test at P34 or P44. Sample sizes are indicated within each bar. Data from each age were obtained from separate cohorts of animals. Genotypes with differing letters differ significantly from each other (p < 0.05, Fisher’s PLSD). See Results for ANOVA details.

Figure 4.

Hom Brattleboro juveniles emit fewer 50 kHz USVs. A–C, Number of all (A), 50 kHz (B), and 22 kHz (C) USVs of male and female Hom, Het, and WT rats during the first 10 min of a 20 min test at P34 or P44. Sample sizes are indicated within each bar. Data from each age were obtained from separate cohorts of animals. Genotypes with differing letters differ significantly from each other (p < 0.05, Fisher’s PLSD); where differences approach significance, the p value is included in parentheses next to the letter representing the appropriate comparison. See Results for ANOVA details.

Figure 5.

Ultrasonic vocalization call types emitted during social behavior testing. A, Percentage of USV call types, as defined by Wright et al. (2010), emitted by male and female Hom, Het, and WT juveniles (P34 or P44) during the first 10 min of a 20 min test; data are combined across sex, genotype, and age. B–G, Representative spectrograms of the most common 50 kHz calls [complex (B), upward-ramp (C), flat (D), step-up (E), and trill (F)] as well as the 22 kHz call (G).

Figure 6.

The quantity and quality of USV calls is altered in Hom Brattleboro rats. A–O, number (A–E), integrated frequency (F–J), and duration (K–O) of type 1 (complex), type 2 (upward-ramp), type 4 (flat), type 7 (step-up), and type 10 (trill) USV calls of male and female Hom, Het, and WT rats during the first 10 min of a 20 min test at P34 or P44. Data from each age were obtained from separate cohorts of animals. Genotypes with differing letters differ significantly from each other (p < 0.05, Fisher’s PLSD); where differences approach significance, the p value is included in parentheses next to the letter representing the appropriate comparison. See Results for ANOVA details.