Gentle stroking stimuli induce affiliative responsiveness to humans in male rats.

Gentle tactile stimuli have been shown to play an important role in the establishment and maintenance of affiliative social interactions. Oxytocin has also been shown to have similar actions. We investigated the effects of gentle stroking on affiliative relationships between humans and rats and the effects of gentle stroking on activation of oxytocin neurons. Male rats received 5-min stroking stimuli from an experimenter every other day for 4 weeks between 3 and 6 weeks of age (S3-6 group), for 4 weeks between 7 and 10 weeks of age (S7-10 group), or for 8 weeks between 3 and 10 weeks of age (S3-10 group). Control rats did not receive stroking stimuli. Rats in the S7-10 and S3-10 groups emitted 50-kHz calls, an index of positive emotion, more frequently during stroking stimuli. Rats in the S3-6, S7-10, and S3-10 groups showed affiliative behaviors toward the experimenter. Oxytocin neurons in the hypothalamic paraventricular nucleus of rats in the S3-6, S7-10, and S3-10 groups were activated following stroking stimuli. These findings revealed that post-weaning repeated stroking stimuli induce an affiliative relationship between rats and humans and activation of oxytocin neurons.

Pup exposure facilitates retrieving behavior via the oxytocin neural system in female mice.

Parental behavior in mammals is innate, but it is also facilitated by social experience, specifically social interactions between the parent and infant. Social interactions with infants also induce the alloparental behavior of virgin animals. Oxytocin (OT) plays an important role in mediating alloparental behavior. Although parental behavior is modulated by the medial preoptic area (MPOA) and adjacent regions, it is unclear how OT acts in these regions as a control mechanism of alloparental behavior promoted by adult-pup interaction. The aim of this study was to investigate the role of OT for facilitating effects of adult-pup interactions on alloparental behavior via neural activity of preoptic area (POA), including MPOA and adjacent area. For this purpose, we conducted behavioral tests and examined the neural activity of the OT system in POA. Virgin female mice that were repeatedly exposed to pups showed shorter retrieving latencies and higher number of c-Fos expressing neurons in POA, particular in lateral preoptic area (LPO) compared to control animals that were exposed to pups only one time. In addition, repeated pup exposure increased the proportion of OT neurons and OTR neurons expressing c-Fos in POA. The concentration of OT also significantly increased in the POA. Finally, infusion of an OT antagonist into the POA area blocked the facilitating effects of repeated pup exposure on retrieving behavior. These results demonstrated that the facilitating effects of repeated pup exposure on alloparental behavior occurred via an organizational role of the OT system.

Activation of hypothalamic oxytocin neurons following tactile stimuli in rats.

Gentle touching or stroking has anxiolytic actions and contributes to the establishment of an intimate relationship between individuals. Oxytocin administration also has anxiolytic actions and facilitates social behaviors. In this study, we examined effects of stroking stimuli on activation of oxytocin neurons and emission of 50-kHz ultrasonic vocalizations, an index of positive emotion, in rats. The number of oxytocin neurons expressing Fos protein was increased in the hypothalamus, especially in the dorsal zone of the medial parvicellular part of the paraventricular nucleus. The number of 50-kHz ultrasonic vocalizations was also increased. These findings suggest that pleasant sensory stimuli activate hypothalamic oxytocin neurons.

Testosterone inhibits facilitating effects of parenting experience on parental behavior and the oxytocin neural system in mice.

Parental behavior in mammals is facilitated by sensory experiences from infant, and by endocrine hormones. However, the interactions between these factors in the parental behavior of nonreproductive adults are not understood. We examined the interactive effects of gonadal hormones and the experience of repeated pup exposure on parental behavior in sexually naive mice. We also compared oxytocin (OT) expression levels in the paraventricular nucleus of the hypothalamus to behavioral outcomes. Clear sex differences were observed in retrieving tests; initial retrieving latency was shorter in females than in males, and 5-time pup exposure shortened retrieving latency in females only. Gonadectomy influenced neither initial retrieving latency nor pup sensitization in females. In contrast, gonadectomy shortened initial retrieving latency and caused pup sensitization in males. Estrogen implants given simultaneously with gonadectomy further shortened the initial retrieving latency in males, but pup sensitization was not affected and occurred in both sexes. In contrast, simultaneous testosterone implants impaired pup sensitization in both sexes. Similar to the results for responsiveness to pups, the number of OT neurons was increased by gonadectomy in males only. In comparison to gonadectomy only, OT neurons were decreased by simultaneous testosterone implants, but were not influenced by estrogen in either sex. Considering the parallel inhibitory effects of testosterone on both pup sensitization and number of OT neurons, we postulate that sex differences in parental responsiveness facilitated by repeated pup exposure were caused by an inhibitory effect of testosterone via the OT neural system in mice.

Pup odor and ultrasonic vocalizations synergistically stimulate maternal attention in mice.

Pup ultrasonic vocalizations (USVs), which are emitted by hypothermic pups, and pup odor are thought to be triggers of maternal behavior in mice. We investigated whether pup odor stimulated maternal responses to pup USVs in mother C57BL/6 mice. Two-choice tests were conducted by introducing mothers into a test cage in which a tube was attached on each long wall, and the duration spent in each tube was compared. Pup USVs were reproduced by an ultrasonic speaker at the tube end. In some cases, cotton with pup odor was also presented at the end of the tube. Compared to no stimuli, mothers did not specifically approach the sole presentation of either reproduced pup USVs or pup odor. However, compared to the sole presentation of pup odor, the simultaneous presentation of pup USVs and odor induced a specific approach response. These results suggested that pup USVs and odor synergistically stimulated maternal behavior. In addition, it was confirmed that mothers approached hypothermic pups emitting pup USVs for longer than anesthetized silent pups. To investigate the underlying neural mechanisms, we observed neural responses to various stimuli with the immunohistochemistry of c-fos expression. In the bed nucleus of the stria terminalis, the medial preoptic area, the central nucleus of the amygdala, and the basolateral amygdala, the numbers of c-fos-positive cells were significantly increased following the simultaneous presentation of pup USVs and odor compared to the presentation of each alone, suggesting that these nuclei were involved in multimodal processing related to maternal behavior.