The majority of sexually inexperienced (virgin) adult laboratory rats of both sexes typically avoid and may sometimes attack (infanticide) infant rat pups when initially exposed to them (Lonstein and De Vries, 2000a; Numan and Insel, 2003). In contrast, the primiparous postpartum lactating female rat that has been exposed to the physiological events of pregnancy and parturition will care for her own or foreign pups (pups from another mother) on day 1 postpartum (Numan and Insel, 2003; Rosenblatt and Lehrman, 1963; Wiesner and Sheard, 1933). Such postpartum females will retrieve the pups to a nest site, lick and groom them, and crouch over them to keep them warm and to nurse them. Under natural conditions, feral rats display a uniparental maternal care system where postpartum females care for their young in a secluded nest site within a burrow; male paternal behavior is not displayed by feral rats (Calhoun, 1963; Lonstein and De Vries, 2000a).

In a prescient review, Kelley (1988) considered the ways in which sexually dimorphic behaviors (one sex shows a particular behavior and the other does not under natural conditions) can occur. One possibility is that the neural mechanisms regulating the behavior are present in one sex and not the other. Another possibility is that the necessary neural mechanisms regulating the behavior are present in both sexes, but the internal physiological events that activate these neural mechanisms are present in one sex but not the other. Kelley used parental behavior in laboratory rats as an example of the latter possibility. Kelley noted that although virgin laboratory rats of both sexes avoid and may attack infant rat pups when initially exposed to them, virgins of both sexes can be sensitized to show parental responses: Constant exposure to young over a series of several days switches virgins of both sexes from avoidance to caring for foreign pups. They will ultimately retrieve pups to a nest and crouch over them in a nursing-like posture even though lactation is not occurring (Rosenblatt, 1967). Under natural conditions virgin males and females are not continuously exposed to pups. Therefore, male rats do not display parental behavior, while females do after they are exposed to the physiological events associated with pregnancy and parturition. Kelley emphasizes, however, that these sensitization experiments on laboratory rats show that the neural circuits regulating parental behavior are present in the brains of both sexes.

In laboratory studies, it has been found that feral virgin house mice (Mus musculus) of both sexes are typically infanticidal when exposed to foreign pups, while postpartum females will care for such pups (Jakubowski and Terkel, 1982; McCarthy and vom Saal, 1985; Parmigiani et al., 1999; Soroker and Terkel, 1988). Research on the responsiveness of virgin female laboratory mice from several inbred and outbred strains sharply contrasts with the findings on virgin female rats and virgin female feral mice. Beginning with the early studies by Leblond (1940), it has been found that a high proportion of virgin females from many, but not all, laboratory strains show near-immediate maternal behavior (sometimes referred to as spontaneous maternal behavior) when exposed to foreign pups in their home cages (Kuroda et al., 2011; Lonstein and De Vries, 2000a; Mei et al., 2023: Numan and Insel, 2003; Stolzenberg and Rissman, 2011), and that the incidence of infanticide is virtually nonexistent (Parmigiani et al., 1999). The majority of virgin females from many of these strains retrieve, groom, and crouch over pups within 15‐30 min after their presentation, although 60 min of pup exposure may be required in some cases. But clearly, several days of sensitization are not required in most strains that have been examined. One can speculate that the genetic changes associated with selective breeding and inbreeding may have liberated the neural mechanisms regulating the prompt onset of maternal responsiveness in many strains of laboratory female mice from strict control by the physiological events associated with pregnancy and parturition, even though maternal responsiveness was not specifically targeted.

In contrast to virgin female laboratory mice, the response of virgin male laboratory mice to pups is variable and dependent on the strain being tested. That is, the percentage of virgin males that either attack pups, ignore pups, or show parental behavior can vary by strain. But in many strains a high level of infant-directed aggression (infanticide) is observed, where 50 % or more of the tested males attack pups (Alsina-Llanes et al., 2025; Lonstein and De Vries, 2000a; Mayer et al., 2019a; Numan and Insel, 2003; Parmigiani et al., 1999; Tachikawa et al., 2013; vom Saal, 1985). It appears that for many strains of inbred and outbred laboratory mice, parental responsiveness is under greater inhibition in virgin males than in virgin females. Importantly, nonparental virgin male laboratory mice can be sensitized to show parental behavior toward pups (Alsina-Llanes et al., 2025), indicating, as in rats, that neural circuits regulating parental behavior are present in both sexes.

Most neurobiological studies on the neural regulation of parental behavior in laboratory mice have used one particular strain more than any other: The inbred C57BL/6 strain. Even when genetically modified mice are used, their genetic background is typically the C57BL/6 genome. Importantly, virgin female mice from this strain show relatively prompt maternal behavior when exposed to pups in their home cages (Stolzenberg and Rissman, 2011; Tsuneoka et al., 2013), while virgin male mice from this strain are highly infanticidal (Alsina-Llanes et al., 2025; Tachikawa et al., 2013).

The primary purpose of this review is to explore what is known about the neural mechanisms that suppress parental behavior in sexually inexperienced laboratory rats and mice. For rats, most of this research has been done on the female. Not surprisingly, since many virgin female mice show spontaneous maternal behavior, the mouse research has focused primarily on the neural mechanisms that suppress parental responsiveness and induce infant-directed attack in virgin male mice (Olazabal and Alsina-Llanes, 2025). In examining the neural circuits that suppress parental responsiveness in female rats and male mice, the degree of commonality in these circuits will be evaluated. Where applicable, research on the neural mechanisms that promote parental responsiveness will also be presented since it is these mechanisms that need to be inactive in nonparental virgins. Finally, research will be reviewed that shows that latent neural circuits that suppress parental behavior can be activated in highly maternal virgin female mice under certain conditions.

Table 1 provides a list of abbreviations used to identify the neural regions referred to in the text of this review.