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.

Dissociation of Puberty and Adolescent Social Development in a Seasonally Breeding Species

“…Vasopressin has long been known to regulate aggression in adult animals [69], and has recently been implicated in play [67,70–72]. Brattleboro rats, which contain a mutation in the vasopressin gene, exhibit lower levels of play than wild type littermates while maintaining the same temporal profile of play development [73], and gonadectomy markedly reduces vasopressin mRNA and/or peptide in the bed nucleus of the stria terminalis, medial amygdala, and their projection areas [74,75]. These findings suggest a gonadal-dependent rather than puberty-independent role for vasopressin.…”

“…Same-sex, same-treatment cagemate pairs were separated and subsequently reunited the following day in a fresh cage, at which point behaviors were recorded using a Sony Handycam video camera (DCR-SR85). This separation paradigm is commonly used to stimulate play behavior at the time of testing [70,73,79,80]. Play and aggressive behaviors were scored from video by an observer unaware of experimental group assignments using JWatcher software (http:/jwatcher.ucla.edu/) or Observer XT12 (Noldus Information Technology Inc.).…”

Neonatal oxytocin and vasopressin manipulation alter social behavior during the juvenile period in Mongolian gerbils

“…(Bester‐Meredith & Marler, ; Taylor et al, ; Veenema, Bredewold, & De Vries, ). Moreover, AVP‐deficient Brattleboro rats exhibit decreased juvenile play behavior and decreased play‐induced vocalizations compared to wild‐types (Paul et al, ). However, modulation of play behavior via OT and AVP in the brain appears to be site‐ and sex‐specific (Bredewold, Smith, Dumais, & Veenema, ; Paul et al, ; Veenema et al, ).…”

Subtle sex differences in vasopressin mRNA expression in the embryonic mouse brain

“…In adult rats and mice, the AVPR1A is commonly found in the somatosensory cortex (SC), olfactory tubercle (OT), nucleus accumbens, lateral septum (LS), hippocampus, amygdala, bed nucleus of the stria terminalis (BNST), hypothalamus, and ventral tegmental area (VTA) . Its presence in these brain regions is known to be important to the modulation of a variety of social behaviors, including aggression, social memory, vocal communication, and social play …”

“…3,4 Its presence in these brain regions is known to be important to the modulation of a variety of social behaviors, including aggression, social memory, vocal communication, and social play. [5][6][7][8] While the vasopressin system is broadly distributed throughout the brain, the amount of AVP, as well as the specifics of its location and the density in AVPR1A expression, varies between sexes. Beyond the PVN and SON, AVP is also produced in several other brain regions, where it tends to be more abundant in males as compared to females.…”