Pleasant touch sensations play a fundamental role in social bonding, yet the neural mechanisms underlying affinity-like behaviors remain poorly understood. Here, we demonstrate that juvenile-adolescent rats, which naturally engage in social play with peers characterized by rough-and-tumble interactions and 50 kHz ultrasonic vocalizations indicating pleasant sensations, develop a strong affinity for human hands through similar playful contact achieved by repeated tickling with human hands. Using this rat with tickling-induced high affinity for human hands, we discovered that repeated tickling mimicking rough-and-tumble play led to increased oxytocin receptor (OTR) expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl). Inhibition of oxytocin signaling in the VMHvl reduced affinity-like behaviors from rats to human hands. These findings suggest that OTR neurons in VMHvl play an important role in the increase in affinity for human hands induced by pleasant touch sensation with human touch-induced play behavior. Based on retrograde and anterograde tracing studies examining the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) as primary sources of oxytocin, we demonstrate that a subset of oxytocin fibers in the VMHvl originate from the SON, suggesting that affinity-like behavior from rats to human hands may be controlled by oxytocin signaling from magnocellular neurons. Together, this work advances our understanding of how oxytocin shapes social behavior and may inform the development of therapeutic strategies to promote positive social interactions.

The ratio of the second and fourth digits (2D:4D) is a morphological marker reflecting fetal exposure to sex steroid hormones. This ratio exhibits sexual dimorphism, with males typically showing a significantly lower ratio than females, which results from higher androgen exposure during the fetal period. While studies in humans have suggested a relationship between sexual orientation and the 2D:4D ratio, this relationship in rodents remains elusive. Here, we investigated this relationship using rats as an experimental model. We found that male rats exhibited significantly shorter 2D length than females, resulting in a lower 2D:4D ratio in males, similar to humans. Observations of sexual behavior revealed that males that ejaculated during the first mating test exhibited shorter 2D length compared to males those that did not ejaculate. When males were classified into two groups based on 2D length (long-2D and short-2D groups), short-2D males were more sexually active than long-2D males. Additionally, only short-2D males showed a preference for female odors. These findings suggest that, in rats, 2D length is a useful morphological marker reflecting sexual activity and preference. Furthermore, they provide evidence supporting the potential use of the 2D:4D ratio as a tool for studying the relationship between sexual orientation and the 2D:4D ratio in humans.

Arginine vasopressin (AVP) and oxytocin (OT) are well-known as neuropeptides that regulate various social behaviors in mammals. However, little is known about their role in mouse female sexual behavior. Thus, we investigated the role of AVP (v1a and v1b) and OT receptors on female sexual behavior. First, we devised a new apparatus, the bilevel chamber, to accurately observe female mouse sexual behavior. This apparatus allowed for a more precisely measurement of lordosis as receptivity and rejection-like behavior (newly defined in this study), a reversed expression of proceptivity. To address our research question, we evaluated female sexual behavior in mice lacking v1a (aKO), v1b (bKO), both v1a and v1b (dKO), and OT (OTRKO) receptors. aKO females showed decreased rejection-like behavior but a normal level of lordosis, whereas bKO females showed almost no lordosis and no change in rejection-like behavior. In addition, dKO females showed normal lordosis levels, suggesting that the v1b receptor promotes lordosis, but not necessarily, while the v1a receptor latently suppresses it. In contrast, although OTRKO did not influence lordosis, it significantly increased rejection-like behavior. In summary, the present results demonstrated that the v1a receptor inhibits proceptivity and receptivity, whereas the v1b and OT receptors facilitate receptivity and proceptivity, respectively.

In mammalian reproduction, sexually active males seek female conspecifics, while estrous females try to approach males. This sex-specific response tendency is called sexual preference. In small rodents, sexual preference cues are mainly chemosensory signals, including pheromones. In this article, we review the physiological mechanisms involved in sexual preference for opposite-sex chemosensory signals in well-studied laboratory rodents, mice, rats, and hamsters of both sexes, especially an overview of peripheral sensory receptors, and hormonal and central regulation. In the hormonal regulation section, we discuss potential rodent brain bisexuality, as it includes neural substrates controlling both masculine and feminine sexual preferences, i.e., masculine preference for female odors and the opposite. In the central regulation section, we show the substantial circuit regulating sexual preference and also the influence of sexual experience that innate attractants activate in the brain reward system to establish the learned attractant. Finally, we review the regulation of sexual preference by neuropeptides, oxytocin, vasopressin, and kisspeptin. Through this review, we clarified the contradictions and deficiencies in our current knowledge on the neuroendocrine regulation of sexual preference and sought to present problems requiring further study.