Effects of pair bonding on parental behavior and dopamine activity in the nucleus accumbens in male prairie voles.

Male parental care is a vital behavior for the development as well as the physical and mental well-being of the young. However, little is known about the neurochemical regulation of male parental behavior, mainly due to the lack of appropriate animal models. In this study, we used the socially monogamous male prairie vole (Microtus ochrogaster) to investigate the effect of pair-bonding experience on paternal behavior and dopamine (DA) signaling in the nucleus accumbens (NAcc) in the brain. We compared sexually naïve males with males that were pair bonded with a female for two weeks. Our data showed that pair-bonded males displayed enhanced paternal behavior, particularly in pup licking/grooming, associated with increased DA type-1 receptor (D1R) protein expression in the NAcc, compared to sexually naïve males. Site-specific brain microdialysis revealed a significant, but transient, increase in DA release in the NAcc associated with pup exposure in both groups of the males. Further, pharmacological blockade of D1R in the NAcc decreased pup licking/grooming in the pair-bonded males. Together, our data demonstrate that pair-bonding experience with a female facilitated male parental behavior via NAcc D1R mediation in male prairie voles.

Postpartum inhibition of ovarian steroid action increases aspects of maternal caregiving and reduces medial preoptic area progesterone receptor expression in female rats.

The rapid peripartum onset of maternal caregiving involves progesterone synergizing with estradiol, but prolonging progesterone exposure past this time can prevent the emergence of mothering. Interestingly, there is a 7-10day-long rise in progesterone during mid-lactation, but its effects on mothering are unknown. Given progesterone's potential to inhibit mothering onset, this mid-lactational rise may contribute to the normal attenuation of caregiving behaviors across lactation. To evaluate this, recently-parturient rats were ovariectomized and caregiving observed from postpartum days (PPD) 7-18. Ovariectomized dams were found to lick, hover over, and nurse in kyphosis more frequently than controls. Ovariectomy also decreased medial preoptic area (mPOA) progesterone receptor (PR) mRNA, which was negatively correlated with pup licking and kyphosis, but it did not affect mPOA levels of oxytocin receptor or vasopressin V1a receptor mRNAs. In a second study, gonadally intact dams were given the PR antagonist, RU 486, and were found to display more kyphosis and less supine nursing compared to controls. Finally, progesterone sensitivity across lactation was examined by measuring numbers of PR immunoreactive (PR-ir) cells in the mPOA, ventral bed nucleus of the stria terminalis (BSTv) and periaqueductal gray (PAG). PR-ir was higher in the mPOA at parturition compared to virgins, while PR-ir in the mPOA and BSTv dropped from parturition to PPD 7 and remained low through PPD 18. The number of PR-ir cells in the PAG was constant. Thus, in addition to their well-known prepartum effects, ovarian hormones limit the display of some maternal behaviors during mid-to-late lactation and contribute to their decline as weaning approaches.

Interaction between postpartum stage and litter age on maternal caregiving and medial preoptic area orexin.

Most maternal caregiving behaviors change across lactation to match the developmental needs of the continuously aging offspring. However, it is mostly unknown whether the dams' postpartum stage or litter age is the primary driving force of these changes. In this study, postnatal day 1 and 8 litters were cross-fostered or in-fostered to postpartum day 1 or 8 dams. Five days later, undisturbed observations of maternal caregiving behaviors were performed on the subsequent two days. We found a main effect of dams' postpartum stage on the frequency that mothers spent with the pups and displayed erect postures over them (hovering over and kyphosis), although it was mostly driven by an interaction between postpartum stage and litter age: early-postpartum dams were in contact with younger litters and in erect postures more often with younger litters compared to later-postpartum dams with younger litters. Additionally, there was an interaction between postpartum stage and litter age on the litter weights because older litters living with later-postpartum dams were heavier than older litters living with early-postpartum dams. There was also an interaction between postpartum stage and litter age on the dams' bodyweight, with early-postpartum dams living with younger litters weighing the least and later-postpartum dams living with younger litters weighing the most. Because activity of the neuropeptide, orexin, within the medial preoptic area (mPOA) has been implicated in maternal nursing and other caregiving behaviors, we measured mPOA levels of orexin-A but it was not affected by postpartum stage or litter age (nor was there an interaction). However, high orexin-A was negatively associated with the frequency of contact with pups and the display of erect postures. These results indicate that changes in caregiving across lactation are driven by endogenous factors in the dams, age-related cues they receive from offspring, and interactions between these factors.

Sex differences in the parental behavior of rodents.

The reproductive strategy of many mammalian species that give birth to altricial young involves intense and prolonged care of their offspring. In most cases, the mother provides all nurturance, but in some cases fathers, older siblings, or unrelated conspecifics participate in parental care. The display of these behaviors by animals other than mothers is affected by numerous factors, including their sex. We herein review the literature on similarities and/or differences between male and female laboratory rodents (rats, mice, voles, gerbils, and hamsters) in their parental responsiveness and discuss how the parental behavior of males and females is influenced by hormones, developmental processes, and prior social experiences. Understanding the mechanisms that generate sex differences in the parental responsiveness of rodents may indicate how similar sex differences in parental care are generated in other mammals.

Maternal behaviour in lactating rats stimulates c-fos in glutamate decarboxylase-synthesizing neurons of the medial preoptic area, ventral bed nucleus of the stria terminalis, and ventrocaudal periaqueductal gray.

Increased activity of the immediate-early gene c-fos can be observed in many areas of the lactating rat brain after dams physically interact with pups and display maternal behaviour. These sites include the medial preoptic area, ventral bed nucleus of the stria terminalis, and the ventrolateral caudal periaqueductal gray, each of which is critical for the normal performance of particular maternal behaviours. The phenotype of cells in these areas that show increased c-fos activity after maternal behaviour, however, is unknown. Via double-label immunocytochemistry, we determined if the population of cells in these sites that express c-fos after maternal behaviour in lactating rats overlaps with the population that expresses the 67,000 mol. wt isoform of glutamate decarboxlyase, the synthesizing enzyme for the inhibitory neurotransmitter GABA. Lactating rats were separated from pups beginning on day 5 postpartum, and 48h later half were allowed to interact with a litter of pups for 60min whereas the other half were not. Dams re-exposed to pups were highly maternal, retrieving and licking them as well as displaying prolonged nursing behaviour that included milk letdown. Both groups of dams had a similar number of 67,000 mol. wt glutamate decarboxylase-immunoreactive cells in each site, although the number of 67,000 mol. wt glutamate decarboxylase-immunoreactive cells per microscopic field was significantly greater in the caudal ventrolateral periaqueductal gray than in the ventral bed nucleus of the stria terminalis, which in turn was greater than the medial preoptic area. In pup-stimulated dams, two to fourfold more Fos-immunoreactive cells were found in these three sites compared with non-stimulated controls. Labeling for Fos immunoreactivity and 67,000 mol. wt glutamate decarboxylase immunoreactivity was heterogeneous within each site. In the medial preoptic area, more Fos-immunoreactive and 67,000 mol. wt glutamate decarboxylase-immunoreactive cells (either single or dual-labeled) were found dorsally than ventrally. In the ventral bed nucleus of the stria terminalis, more Fos-immunoreactive and 67,000 mol. wt glutamate decarboxylase-immunoreactive cells were found medially than laterally. Within the caudal ventrolateral periaqueductal gray, 67,000 mol. wt glutamate decarboxylase-immunoreactive labeling was greatest ventromedially, while high numbers of Fos-immunoreactive nuclei were found both ventromedially and ventrolaterally. In pup-stimulated dams, more than half (53% in the medial preoptic area, 59% in the ventral bed nucleus of the stria terminalis, and 61% in the caudal ventrolateral periaqueductal gray) of the total population of Fos-immunoreactive cells also expressed 67,000 mol. wt glutamate decarboxylase. These results suggest that many of the neurons in these sites that show elevated c-fos activity after maternal behaviour are either local inhibitory interneurons or provide inhibitory input to other neural sites. These inhibitory mechanisms may be critical for the display of postpartum nurturance, possibly facilitating maternal behaviour by removing tonic inhibition on sites necessary for maternal responding or by restricting activity in neural sites that inhibit it.

GABA(A) receptor regulation of kyphotic nursing and female sexual behavior in the caudal ventrolateral periaqueductal gray of postpartum rats.

Bilateral lesions of the ventrolateral caudal periaqueductal gray inhibit lordosis and kyphosis, the postures of female sexual receptivity and maternal nursing that are characterized respectively by dorsoflexion and ventroflexion of the spinal column. These lesions also inhibit the solicitation behaviors that accompany lordosis, but they do not impair retrieval or licking of pups. We tested the hypothesis that reproductive behaviors affected by these lesions are tonically inhibited by activity of the GABA(A) receptor via site-specific manipulations of receptor activity. Rats were bilaterally implanted during pregnancy with guide cannulae aimed at the caudal periaqueductal gray and ovariectomized on day 1 postpartum. Microinfusions (0.25 microl/side) of saline or drug took place on days 5 and 7 postpartum into the dorsolateral column and on days 9 and 11 into the ventrolateral column. Five minutes post-infusion dams were reunited with their pups and their maternal behavior was observed for 30 min. Feminine sexual behaviors were evaluated post-weaning after another set of microinfusions in the ventrolateral caudal periaqueductal gray. Potential facilitation of kyphosis and lordosis was tested with the GABA(A) antagonist bicuculline (15 ng/side) during sub-threshold conditions, i.e., non-suckling pups or sub-threshold ovarian hormone dosages; potential inhibition of these postures was tested with the GABA(A) agonist muscimol (125 ng/side) during optimal conditions, i.e., suckling pups or supra-threshold ovarian hormone treatments. Dorsolateral drug manipulations were ineffective. In the ventrolateral periaqueductal gray bicuculline significantly increased and muscimol significantly decreased kyphosis, lordosis, and sexual solicitations compared with saline. Retrieval and licking of pups were not altered by GABA(A) manipulations. These findings suggest that the reproductive postures of female rats, lordosis and kyphosis, as well as sexual solicitations, are tonically inhibited by the neurotransmitter GABA within the ventrolateral caudal periaqueductal gray in the midbrain. In contrast, retrieval and licking of pups appear to be under separate neurochemical or neuroanatomical control, or both. Further, this tonic inhibition is likely relieved by excitatory somatosensory inputs to this site, from mounting and suckling respectively.

Forebrain expression of c-fos due to active maternal behaviour in lactating rats.

To reveal brain sites simultaneously active during the expression of maternal behaviour in lactating rats, we used immunocytochemical visualization of the nuclear protein product Fos of the immediate-early gene c-fos as a marker of neuronal activity. After a 48 h separation from their litter, day 7 postpartum dams received a 1 h period of physical interaction with pups either capable or incapable of suckling, inaccessible pups in a wire-mesh box, an empty box, or no stimulation. Physical interaction with pups elicited high levels of pronurturant maternal behaviour (retrieval, licking, mouthing), and suckling elicited nursing behaviour as well. Exposure to the box, with or without pups, elicited high levels of investigatory sniffing, self-grooming, and general activity. Distal stimulation from pups did not differentially activate Fos in any of 20 sites, including olfactory-processing structures such as the piriform cortex and medial amygdala. Physical interaction with pups, with or without suckling, elicited higher levels of Fos-immunoreactive nuclei than that of other conditions in numerous sites, including many previously implicated in maternal behaviour (medial preoptic nucleus, nucleus accumbens, lateral septum, lateral habenula, and the bed nucleus of the stria terminalis). Similar group patterns of Fos expression also occurred in sites not previously implicated in maternal behaviour (somatosensory cortex and paraventricular thalamic nucleus). Interaction with nonsuckling pups elicited the highest levels of Fos in the cortical amygdala, whereas suckling did not activate higher Fos than nonsuckling interaction in any site included in this report, including hypothalamic nuclei involved in lactation (paraventricular, supraoptic, and arcuate). There was little or no Fos in cingulate cortex, olfactory tubercle, medial septum, medial habenula, or ventromedial hypothalamus. These data suggest that trigeminal stimuli received by lactating rats during the performance of pronurturant maternal behaviour promote cellular activity resulting in neuronal expression of c-fos in many forebrain sites including the medial preoptic nucleus, several sites connected with it that are part of the mesotelencephalic dopamine system, and in the somatosensory cortex. In contrast, in these forebrain sites suckling does not elicit greater levels of Fos than that seen in nonsuckled rats and distal stimuli from pups are ineffective in increasing Fos levels compared with non-stimulated controls.

Neural mediation of nursing and related maternal behaviors.

Nursing is the behavioral concomitant of lactation and the most generalizable maternal behavior across mammals. In lactating rats nursing often occurs in the kyphotic (upright crouched) posture; like the neuroendocrine determinants of milk synthesis and release, kyphosis requires suckling by the young. The dam's active pronurturant behaviors, such as retrieval and licking of pups, requires perioral somatosensory stimulation, which is often a precursor of kyphosis as well, and is inhibited by suckling. The sequential nature of maternal behaviors and the dissociations in their somatosensory regulation are critical to understanding their neural mediation, as exemplified by our recent work in lactating rats. We found that the caudal lateral and ventrolateral midbrain periaqueductal gray (cPAGl,vl) is a sensorimotor integration site for the kyphotic nursing posture. Destruction of the cPAGl,vl, or increased activity of the inhibitory neurotransmitter GABA within it, severely reduced kyphosis, increased nursing in more atypical postures, and had little or no effect on pronurturance. Various forebrain sites are known to mediate retrieval and licking of pups. Inhibition of dopaminergic activity in the nucleus accumbens of dams via microinfusions of a mixed D1/D2 dopamine receptor antagonist, cis-flupenthixol (FLU), dose-dependently reduced these active behaviors, while increasing nursing duration. Retrieval was inhibited, however, only by infusions of FLU that included the nucleus accumbens shell, which is reciprocally connected with other sites implicated in retrieval of pups. Thus, maternal behavior is not a unitary process but rather a complex category consisting of sequential behavioral components that have their own sensory and neural determinants.

Immunocytochemical investigation of nuclear progestin receptor expression within dopaminergic neurones of the female rat brain.

Progesterone influences most processes involved in female reproduction, including ovulation, sexual behaviour, pregnancy, parturition, lactation and maternal behaviour. One neurotransmitter through which progesterone might regulate many of these functions is dopamine. To determine where in the brain progesterone might alter dopaminergic activity necessary for these and other processes in rats via cell nuclear progestin receptors, ovariectomized rats were injected subcutaneously with either 4 micro g oestradiol benzoate to induce high levels of hypothalamic progestin receptor expression, or oil, and perfused 48 h later. Dual-label immunocytochemistry was used to visualize cells having immunoreactivity (ir) for progestin receptors and tyrosine hydroxylase, a rate-limiting enzyme for dopamine synthesis. Many cells containing both progestin receptor-ir and tyrosine hydroxylase-ir were found throughout the periventricular hypothalamus of oestradiol-treated females. Conversely, very few cells in the hypothalamus of oil-treated controls contained progestin receptor-ir and, consequently, few dual-labelled cells were found in this group. The greatest percentage of tyrosine hydroxylase immunoreactive cells expressing progestin receptors in oestradiol-treated females was in, or near, the arcuate nucleus (A12 group), where up to 55% of tyrosine hydroxylase-expressing cells coexpressed progestin receptors. Notably, dual-labelled cells in oestradiol-treated females were also found more rostrally than previously reported, with approximately 15-20% of tyrosine hydroxylase-ir cells in the preoptic area/anterior hypothalamus (A14 group) also containing progestin receptor-ir. No dual-labelled cells were found for either group in the posterodorsal hypothalamus (A11 group), zona incerta (A13 group), retrorubral field (A8 group), ventral tegmental area (A10 group) or substantia nigra (A9 group) because little or no progestin receptor-ir was found in these sites. These data provide new information about the neural substrate where progesterone might regulate dopamine release in the preoptic area/anterior hypothalamus. Using more sensitive techniques than those used previously, they also confirm the relationship between progestin receptor and tyrosine hydroxylase in the arcuate nucleus, which could be important for the regulation of prolactin release throughout the female reproductive cycle. Additionally, although progesterone alters mesolimbic and nigrostriatal dopamine release, and the numerous behaviours that these pathways influence, these data again suggest that it does not do so via nuclear progestin receptor in dopaminergic cells of the ventral tegmental area and substantia nigra.

Sex differences in the parental behaviour of adult virgin prairie voles: independence from gonadal hormones and vasopressin.

Sexually and parentally experienced prairie voles display robust biparental care of pups that is similar between the sexes. Little is known, however, about possible sex differences in the parental behaviours of sexually inexperienced prairie voles. Parental behaviour of adult virgin male and female prairie voles was examined in sham-operated and gonadectomized subjects treated with vehicle or oestradiol. Since arginine-vasopressin (AVP) has been suggested to stimulate parental behaviour in sexually inexperienced males, neural AVP immunoreactivity (AVP IR) was quantified. Most sham-operated and castrated males displayed high levels of parental behaviour (9/9 controls, 6/9 castrates) during a 15-min exposure to pups 4 weeks after surgery, and few behavioural differences were seen between groups. Conversely, almost all gonadally intact (8/9) and gonadectomized (8/9) females attacked pups. Implantation of a 0.1-mg pellet of oestradiol immediately after gonadectomy had little effect on males (9/9 parental), whereas most (5/9) oestradiol-treated females acted maternally. AVP-immunoreactive (AVP-ir) fibre density in the lateral septum (LS) and lateral habenula (LHb), expressed by the number of pixels that covered AVP-ir fibres during computerized optical density analysis, was greater in males than females, was non-significantly reduced in castrated males, and doubled in the LS of oestradiol-treated females. In a second experiment, males tested 8 weeks after similar manipulations remained highly parental though castrated males had almost no AVP-ir fibres in the LS and LHb. Levels of AVP IR in males treated with oestradiol were similar to those observed in intact males. A dramatic sex difference therefore exists in the parental behaviour of adult sexually naive prairie voles which cannot be explained by sex differences in gonadal hormones. Because both castrated and intact males were highly parental, even though castrates had virtually no AVP-ir in the LS or LHb, AVP does not appear to be crucial for their responsiveness toward pups.

Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats.

Exposure to gonadal hormones during perinatal life influences later behavior. The finding that sex differences exist in progestin receptor expression in the perinatal rat brain suggests differential sensitivity of male and female brains to progesterone (C. K. Wagner, A. N. Nakayama, & G. J. De Vries, 1998). Because these sex differences are in neural sites that influence sexually differentiated sexual, parental, and fearful behaviors in adults, this study examined the effects of administering the progestin receptor antagonist RU486 for the first 10 days after birth on these behaviors in adulthood. Neonatal RU486 significantly reduced sexual behavior in males but did not impair reproduction in females. Neonatal RU486 did not affect parental responses of virgin rats exposed to pups (sensitization) but reduced fear in the elevated plus-maze in both sexes. Treatment of pups with RU486 affected neither mother-litter interactions nor plasma testosterone levels in males during or after treatment. These results suggest that neonatal exposure to progesterone, in addition to androgens and estrogens, influences behavioral development in rats.

Functions of the caudal periaqueductal gray in lactating rats: kyphosis, lordosis, maternal aggression, and fearfulness.

Severe impairment of the kyphotic nursing posture in lactating rats found previously after prepartum lesions of the caudal intercollicular periaqueductal gray (cPAG-x) was confirmed and was extended to a continuous 24-hr period. Litters of cPAG-x dams gained approximately 10% less weight postnatally than controls, which was in part related to their dams' compensatory prone nursing posture that was ineffective for milk letdown. Sexual proceptivity and receptivity (lordosis) during the postpartum estrus were virtually eliminated in subjects with relatively large bilateral cPAG lesions. The doubling of maternal attacks toward a male intruder after lesioning was also confirmed and was related to reduced fearfulness in an elevated plus-maze. Thus, the cPAG plays a multifaceted role in parturient rats; it is involved in the mediation of nursing, sexual, aggressive, and fear behaviors.

Influence of gonadal hormones on the development of parental behavior in adult virgin prairie voles (Microtus ochrogaster).

Prairie voles (Microtus ochrogaster) are a socially monogamous species and both sexes are parental after the birth of pups. In contrast, sexually inexperienced adult prairie voles differ in their behavior towards pups such that virgin males are paternal whereas virgin females are often infanticidal. To test whether there exists a discrete perinatal 'sensitive period' during which gonadal hormones influence this behavior, and to distinguish between the relative contributions of estrogenic and androgenic mechanisms to this influence, prairie voles were exposed to testosterone propionate (TP), the anti-androgen flutamide, or the aromatase inhibitor 1,4,6-androstatriene-3,17-doine (ATD) either prenatally via their pregnant dam for the last 15-19 days of the 22-day gestational period or postnatally on days 1-7. None of the treatments altered the high paternal responsiveness of males or the high infanticide rate in females when compared with controls. Females exposed prenatally to ATD, however, had levels of parental behavior that were significantly higher than the lowest levels observed in prenatally TP-treated females. These results suggest that sex differences in the parental behavior of adult virgin prairie voles are not generated exclusively by androgenic or estrogenic mechanisms during a restricted prenatal or early postnatal 'sensitive period' and that the parental behavior of virgin females may be more susceptible to any influence of gonadal hormones during development than males.

Site and behavioral specificity of periaqueductal gray lesions on postpartum sexual, maternal, and aggressive behaviors in rats.

Bilateral electrolytic lesions of the lateral and ventrolateral caudal periaqueductal gray (cPAGl,vl) of lactating rats are known to severely reduce suckling-induced kyphosis (upright crouched nursing), which is necessary for maximal litter weight gains, and impair sexual behavior during the postpartum estrous, while heightening nursing in other postures and attacks on unfamiliar adult male intruders. In the present report, the site specificity of the cPAG with respect to the control of these behaviors was determined by comparing lesions of the cPAGl,vl with similarly sized lesions within the rostral PAG (rPAG) and surrounding mesencephalon. The previously seen effects of prepartum cPAGl,vl lesions on kyphotic nursing, sexual proceptivity and receptivity, maternal aggression, and daily litter weight gains were replicated. Additionally, the post-lesion facilitation of aggression was found to be behaviorally specific, first by being directed toward an adult, but not to a nonthreatening juvenile male rat, and second, by requiring the recent presence of the pups, being eliminated or decreased 24 h after removal of the litter. Damage to the rPAG did not affect nursing or sexual behaviors, and had only a minimal effect on maternal aggression. Lesions of the rPAG, however, greatly impaired the dams' ability to rapidly release pups held in the mouth, but not to pick them up or carry them directly to the nest during retrieval. Separate regions of the PAG, therefore, are differentially involved in the control of specific components of behaviors in lactating rats.

Intracellular preoptic and striatal monoamines in pregnant and lactating rats: possible role in maternal behavior.

In many mammals, hormonal fluctuations during pregnancy and parturition produce neurochemical events that are necessary for the transition from a non-maternal state to a maternal state that occurs when infants are born. However, the nature of these events is mostly unknown. We investigated whether changes in dopamine (DA) and serotonin (5-HT) activity within the preoptic area (POA) and striatum, neural sites important for some maternal behaviors, could be part of this process. Female rats were sacrificed as either diestrus virgins, on pregnancy day 10 or 20, on the day of parturition, or on day 7 or 17 of lactation. Bilateral tissue punches from the POA, dorsolateral striatum (ST(dl)), and nucleus accumbens (NA) were obtained and levels of intracellular DA and 5-HT analyzed with high-performance liquid chromatography with electrochemical detection (HPLC-EC). In the POA, DA was high in virgins and during early pregnancy, lowest on the day of parturition, and very high during lactation. Although there were no changes in the DOPAC to DA ratio (i.e., turnover), DOPAC levels also followed this pattern. 5-HT turnover in the POA was lower in virgins compared to other groups. In the ST(dl), DA turnover was highest during late pregnancy and on the day of parturition, while no changes in 5-HT measures were found. No significant effects were found in the NA. Therefore, decreased DAergic activity in the POA and increased DAergic activity in the ST(dl) occurs around parturition, the time when maternal behavior emerges, and may influence its onset.

Comparison of the parental behavior of pair-bonded female and male prairie voles (Microtus ochrogaster).

The behavior of primiparous lactating prairie voles (Microtus ochrogaster) and their mates individually interacting with pups was continuously assessed for 45 min after a 2-h parent-litter separation on days 3-4 and 10-11 postpartum. Both sexes were highly parental after reunion with the young, and their general pattern of behavior consisted of bouts of quiescence interspersed with bursts of heightened activity. Lactating females spent more time than males in contact with pups, and more time being quiescent, most often in the kyphotic (upright crouched) nursing posture. Even in the absence of nipples upon which the pups could suckle, males also displayed kyphosis, although for shorter durations than females. Males spent more time, however, huddled over the litter in a hunched position than their mates. In accordance with their decreased quiescence, male voles licked and carried pups more and were more exploratory than females. Compared with the first week postpartum, bouts of kyphosis were shorter during the second week postpartum for both sexes, while laying prone on the pups increased. Males spent less time licking and more time carrying older pups than younger ones, and were more exploratory during the second week postpartum. Sex differences in the parental behavior of prairie voles may reflect differences in the somatosensory stimulation that females and males receive from pups. Furthermore, the display of kyphosis by male voles indicates that the sensorimotor organization of this posture in voles differs from that of lactating rats, which require suckling stimulation for its regulation.

Social influences on parental and nonparental responses toward pups in virgin female prairie voles (Microtus ochrogaster).

Pair-bonded prairie voles (Microtus ochrogaster) are biparental after the birth of pups. However, whereas most adult virgin males are parental, most virgin females are not. In 6 experiments, influences on the parental behavior of virgin female prairie voles were examined. It was found that (a) young virgin females were more maternal than older females, (b) the postweaning sex ratio of cage-mates did not affect females' responses to pups, (c) females raised to adulthood with their parents and younger siblings present were highly parental, (d) 48-hr exposure to pups beginning at weaning increased some aspects of later maternal responding, (e) rearing to adulthood with the parents even in the absence of younger siblings also increased females' maternal responding, and (f) the increase was seen only if both parents were present. Continued parental presence promotes alloparental behavior, possibly important if daughters do not disperse from the natal nest.

Differential postpartum sensitivity to the anxiety-modulating effects of offspring contact is associated with innate anxiety and brainstem levels of dopamine beta-hydroxylase in female laboratory rats.

In female mammals, the postpartum period involves dramatic shifts in many socioemotional behaviors. This includes a suppression of anxiety-related behaviors that requires recent physical contact with offspring. Factors contributing to differences among females in their susceptibility to the anxiety-modulating effect of offspring contact are unknown, but could include their innate anxiety and brain monoaminergic activity. Anxiety behavior was assessed in a large group of nulliparous female rats and the least-anxious and most-anxious tertiles were mated. Anxiety was assessed again postpartum after females were permitted or prevented from contacting their offspring 4 h before testing. Levels of dopamine ß-hydroxylase (DBH, norepinephrine synthesizing enzyme) and tryptophan hydroxylase-2 (TPH2, serotonin synthesizing enzyme) were measured in the brainstem and dorsal raphe, respectively. It was found that anxiety-related behavior in the two groups did not differ when dams were permitted contact with offspring before testing. Removal of the offspring before testing, however, differentially affected anxiety based on dams' innate anxiety. Specifically, dams reverted back to their pre-mating levels of anxiety such that offspring removal slightly increased anxiety in the most-anxious females but greatly lowered anxiety in the least-anxious females. This reduction in anxiety in the least-anxious females after litter removal was associated with lower brainstem DBH. There was no relationship between females' anxiety and dorsal raphe TPH2. Thus, a primary effect of recent contact with offspring on anxiety-related behavior in postpartum rats is to shift females away from their innate anxiety to a more moderate level of responding. This effect is particularly true for females with the lowest anxiety, may be mediated by central noradrenergic systems, and has implications for their ability to attend to their offspring.

Attenuated orexinergic signaling underlies depression-like responses induced by daytime light deficiency.

Light has profound effects on mood, as exemplified by seasonal affective disorder (SAD) and the beneficial effects of bright light therapy. However, the underlying neural pathways through which light regulates mood are not well understood. Our previous work has developed the diurnal grass rat, Arvicanthis niloticus, as an animal model of SAD (Leach et al., 2013a,b). By utilizing a 12:12-h dim light:dark (DLD) paradigm that simulates the lower light intensity of winter, we showed that the animals housed in DLD exhibited increased depression-like behaviors in the forced swim test (FST) and sweet solution preference (SSP) compared to animals housed in bright light during the day (BLD). The objective of the present study was to test the hypothesis that light affects mood by acting on the brain orexinergic system in the diurnal grass rat model of SAD. First, orexin A immunoreactivity (OXA-ir) was examined in DLD and BLD grass rats. Results revealed a reduction in the number of OXA-ir neurons in the hypothalamus and attenuated OXA-ir fiber density in the dorsal raphe nucleus of animals in the DLD compared to those in the BLD group. Then, the animals in BLD were treated systemically with SB-334867, a selective orexin 1 receptor (OX1R) antagonist, which led to a depressive phenotype characterized by increased immobility in the FST and a decrease in SSP compared to vehicle-treated controls. Results suggest that attenuated orexinergic signaling is associated with increased depression-like behaviors in grass rats, and support the hypothesis that the orexinergic system mediates the effects of light on mood.

Emotion and mood adaptations in the peripartum female:complementary contributions of GABA and oxytocin.

Peripartum hormones and sensory cues from young modify the maternal brain in ways that can render females either at risk for, or resilient to, elevated anxiety and depression. The neurochemical systems underlying these aspects of maternal emotional and mood states include the inhibitory neurotransmitter GABA and the neuropeptide oxytocin (OXT). Data from laboratory rodents indicate that increased activity at the GABA(A) receptor contributes to the postpartum suppression of anxiety-related behaviour that is mediated by physical contact with offspring, whereas dysregulation in GABAergic signalling results in deficits in maternal care, as well as anxiety- and depression-like behaviours during the postpartum period. Similarly, activation of the brain OXT system accompanied by increased OXT release within numerous brain sites in response to reproductive stimuli also reduces postpartum anxiety- and depression-like behaviours. Studies of peripartum women are consistent with these findings in rodents. Given the similar consequences of elevated central GABA and OXT activity on maternal anxiety and depression, balanced and partly reciprocal interactions between these two systems may be essential for their effects on maternal emotional and mood states, in addition to other aspects of postpartum behaviour and physiology.