An acute dose of intranasal oxytocin rapidly increases maternal communication and maintains maternal care in primiparous postpartum California mice

Maternal-offspring communication and care are essential for offspring survival. Oxytocin (OXT) is known for its role in initiation of maternal care, but whether OXT can rapidly influence maternal behavior or ultrasonic vocalizations (USVs; above 50 kHz) has not been examined. To test for rapid effects of OXT, California mouse mothers were administered an acute intranasal (IN) dose of OXT (0.8 IU/kg) or saline followed by a separation test with three phases: habituation with pups in a new testing chamber, separation via a wire mesh, and finally reunion with pups. We measured maternal care, maternal USVs, and pup USVs. In mothers, we primarily observed simple sweep USVs, a short downward sweeping call around 50 kHz, and in pups we only observed pup whines, a long call with multiple harmonics ranging from 20 kHz to 50 kHz. We found that IN OXT rapidly and selectively enhanced the normal increase in maternal simple sweep USVs when mothers had physical access to pups (habituation and reunion), but not when mothers were physically separated from pups. Frequency of mothers’ and pups’ USVs were correlated upon reunion, but IN OXT did not influence this correlation. Finally, mothers given IN OXT showed more efficient pup retrieval/carrying and greater total maternal care upon reunion. Behavioral changes were specific to maternal behaviors (e.g. retrievals) as mothers given IN OXT did not differ from controls in stress-related behaviors (e.g. freezing). Overall, these findings highlight the rapid effects and context-dependent effect a single treatment with IN OXT has on both maternal USV production and offspring care.

Environmental enrichment delays the development of stereotypic behavior and reduces variability in behavioral experiments using California mice (Peromyscus californicus)

Domesticated mice and rats have shown to be powerful model systems for biomedical research, but there are cases in which the biology of species is a poor match for the hypotheses under study. The California mouse (Peromyscus californicus) has unique physiological and behavioral traits and has emerged as a powerful model for studying sex differences in the biology of psychiatric disease, which is particularly relevant considering the new NIH guidelines that require the inclusion of sex as a biological variable. Despite its growing role in preclinical research, there is a lack of studies assessing species-specific housing needs, which presents a challenge for research facilities seeking to ensure good welfare and obtaining high-quality experimental data. Indeed, captive California mice present a high prevalence of stereotypic backflipping behavior, a common consequence of suboptimal housing and a potential source of experimental outcome variability. Using three different cage systems, the present studies show that increasing housing space as well as social and environmental complexity can delay the development of stereotypic behavior in male and female California mice. Critically, this reduction in stereotypy is accompanied by increased effect sizes of stress in an established model for social anxiety. These results suggest that increased cage size and enrichment could enhance welfare in California mice while simultaneously increasing the quality of behavioral experiments.

Pubertal Androgens Reduce the Effects of Social Stress on Anxiety-related Behaviors in California Mice

Adolescence is an important developmental period during which anxiety-related behaviors differentiate in males and females. In humans anxiety prevalence increases to a greater degree in women than men after puberty, but the mechanism is unknown. We used social defeat stress to model anxiety behaviors in California mouse, a species in which aggressive females allow for comparison of social anxiety behaviors across sex. Adult female California mice show reduced social approach and increased social vigilance after exposure to stress, while these changes are weaker in males. Here we show that in juveniles, social defeat reduces social approach and increases social vigilance in both males and females. Next, we show that prepubertal castration sensitizes adult males to social defeat. However, when pubertal castration was paired with either testosterone or dihydrostesterone replacement, effects of defeat on social approach and vigilance were blunted in adult males. We also showed that effects of defeat on social behavior in juveniles were oxytocin receptor dependent, as has been described for adult females. This work highlights the importance of pubertal testosterone to the development of sex differences in anxiety behavior, and provides evidence that androgen receptors play an important role in the development of neural circuits of anxiety.

An acute dose of intranasal oxytocin rapidly increases maternal communication and maintains maternal care in primiparous postpartum California mice

Maternal-offspring communication and care are essential for offspring survival. Oxytocin (OXT) is known for its role in initiation of maternal care, but whether OXT can rapidly influence maternal behavior or ultrasonic vocalizations (USVs; above 50 kHz) has not been examined. To test for rapid effects of OXT, California mouse mothers were administered an acute intranasal (IN) dose of OXT (0.8 IU/kg) followed by a separation test with three phases: habituation with pups in a new testing chamber, separation via a wire mesh, and finally reunion with pups. We measured maternal care, maternal USVs, and pup USVs. In mothers, we primarily observed simple sweep USVs, a short downward sweeping call around 50 kHz, and in pups we only observed pup whines, a long call with multiple harmonics ranging from 20 kHz to 50 kHz. We found that IN OXT rapidly and selectively enhanced the normal increase in maternal simple sweep USVs when mothers had physical access to pups (habituation and reunion), but not when mothers were physically separated from pups. Maternal-pup USVs were correlated upon reunion, but IN OXT did not influence this correlation. Finally, mothers given IN OXT showed a more positive change in retrievals/carrying and greater total maternal care upon reunion. Behavioral changes were specific to maternal behaviors (e.g. retrievals) as mothers given IN OXT did not differ from controls in stress-related behaviors (e.g. freezing). Overall, these findings highlight the rapid effects and context-dependent effect a single dose of IN OXT has on both maternal USV production and offspring care.