Paternal behavior is associated with central neurohormone receptor binding patterns in meadow voles (Microtus pennsylvanicus)

Paternal and nonpaternal voles (microtus) have different arginine-vasopressin (AVP) and oxytocin (OT) receptor patterns in the extended amygdala, a neural pathway associated with parental behavior. Using receptor autoradiography, the authors examined whether AVP and OT receptor patterns were associated with facultative paternal behavior in either sexually and parentally inexperienced or experienced meadow voles (Microtus pennsylvanicus). Experienced, in contrast to inexperienced, males had less AVP binding in the lateral septum (LS), more AVP binding in the anterior olfactory nucleus (AON), and more OT binding in the AON, bed nucleus of the stria terminalis, LS, and lateral amygdala. Thus, specific AVP receptor patterns, which co-occur with paternal care in consistently paternal voles, also may be associated with paternal care (when present) in typically nonpaternal species. This study also demonstrated a possible relationship between OT receptor patterns and paternal state in male mammals.     

Exogenous melatonin administration affects self-grooming and conspecific odor preferences in long-photoperiod meadow voles (Microtus pennsylvanicus)

For meadow voles, Microtus pennsylvanicus, seasonal differences exist in self-grooming and in odor preferences for conspecifics, two behaviors which facilitate sexual interactions in this species. Both behaviors are mediated by photoperiodically-induced changes in circulating gonadal steroid hormone titers which, in turn, can be transduced by the duration of the melatonin signal that a seasonally breeding animal receives. The goal of this study was to determine whether exogenous melatonin administration affects circulating gonadal steroid hormone titers in meadow voles, and whether it influences their odor preferences and self-grooming behavior to same- and opposite-sex conspecifics. Long-photoperiod voles that did not receive exogenous melatonin had higher testosterone (males) and estradiol (females) titers than did short-photoperiod voles and long-photoperiod voles treated with melatonin for 12 weeks; the latter had similar estradiol and testosterone titers. Long-photoperiod voles that did not receive melatonin preferred the scent marks of long-photoperiod opposite-sex conspecifics and spent more time self-grooming in response to their odors than those of either long-photoperiod same-sex, short-photoperiod same-sex, or short-photoperiod opposite-sex conspecifics. Long-photoperiod voles that received melatonin, however, no longer preferred the marks of long-photoperiod opposite-sex conspecifics and no longer spent more time self-grooming in response to their odors, not unlike the odor preferences and self-grooming behavior of short-photoperiod voles. As a whole, the data suggest that the duration of the melatonin signal is likely involved in mediating the photoperiodically-induced changes in gonadal steroid hormones that mediate a meadow vole's odor preferences for opposite-sex conspecifics and its self-grooming response to those marks.     

Interaction of photoperiod and testes development is associated with paternal care in Microtus pennsylvanicus (meadow voles)

During the summer breeding season, free-living meadow voles do not engage in paternal care. However, in fall when female territoriality declines, social nesting and breeding activity may overlap and adult males nest with females and young. In the laboratory, meadow voles housed under short day (SD) lengths exhibit more and better quality paternal care than those housed under long day (LD) lengths. This observation is commensurate with the hypothesis that SD paternal care may increase fitness by decreasing pup mortality during colder months. However, SD males also demonstrate variability in paternal care. We hypothesize that this variability may be due to male fertility status; SD infertile males, incapable of siring offspring, should be less likely to care for pups than fertile males, for whom paternal care may confer fitness benefits. The goal of this experiment was to determine whether paternal behavior differed between fertile LD males, fertile SD males (i.e. males that were gonadally photoperiod-unresponsive to SD lengths), and infertile SD males (i.e. males that were gonadally photoperiod-responsive to SD lengths), as indexed by paired testes weights and behavioral evaluation. Fertile SD males exhibited proportionally more paternal behavior than infertile SD males or fertile LD males, which did not differ from each other. Fertile SD males also exhibited paternal behavior faster, spent more time in contact with pups, and engaged in longer and more frequent bouts of pup-directed grooming and huddling than either infertile SD males or fertile LD males. Collectively, these data suggest that photoperiod and fertility status may interact to exert both inhibitory and permissive control over the expression of paternal behavior in adult meadow voles.     

The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster)

This study compared the effects of centrally administered oxytocin (OT) and arginine vasopressin (AVP) on partner preference formation and social contact in male and female prairie voles (Microtus ochrogaster). After 1 hr of cohabitation and pretreatment with either AVP or OT, both males and females exhibited increased social contact and significant preference for the familiar partner. After pretreatment with either an OT receptor antagonist (OTA) or an AVP (V1a) receptor antagonist (AVPA), neither OT nor AVP induced a partner preference. In addition, treatment with OT+OTA or AVP+AVPA was associated with low levels of social contact in both sexes. Either AVP or OT is sufficient to facilitate social contact if either the OT or AVP receptor is available. However, the formation of partner preferences may require access to both AVP and OT receptors.     

The role of prolactin and testosterone in mediating seasonal differences in the self-grooming behavior of male meadow voles, Microtus pennsylvanicus

Self-grooming in response to the odors of conspecifics is a form of olfactory communication among meadow voles. The amount of time meadow voles spend self-grooming when they encounter the odors of conspecifics varies seasonally, with males targeting the odors of reproductively active females only during the breeding season. Other odor related behaviors in male voles such as odor preferences for conspecifics and the attractiveness of their odors to conspecifics vary seasonally as well. For male meadow voles, these behaviors are mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers. The objective of this study was to determine whether seasonal differences in the amount of time male meadow voles self-groom in response to odors of conspecifics are mediated by seasonal rhythms in their circulating T and PRL titers. We tested the hypothesis that high titers of both T and PRL are necessary for reproductively active (long-photoperiod; LP) males and sufficient for reproductively quiescent (short-photoperiod; SP) male voles to spend more time self-grooming in response to odors of LP females than to those of other conspecifics. Results of this study demonstrate that high titers of PRL and T are necessary for LP male meadow vole to self-groom more in response to odors of LP females as compared to those of other conspecifics, but were not sufficient to induce SP males to preferentially self-groom to odors of LP females. The endocrine control of self-grooming by LP males appears to depend upon high titers of both PRL and T, which matches the endocrine mediation of other odor related behaviors in male voles. In contrast, the endocrine tissues that underlie self-grooming in SP male meadow voles appear to be refractory to the effects of LP-equivalent titers of PRL and T.     

Developmental exposure to oxytocin facilitates partner preferences in male prairie voles (Microtus ochrogaster)

The authors investigated the effects of postnatal manipulations of oxytocin (OT) on the subsequent tendency to form a partner preference in male prairie voles (Microtus ochrogaster). Neonatally, males received either an injection of OT, an oxytocin antagonist (OTA), 0.9% saline vehicle, or handling without injection. As adults, males were tested for partner preference following 1 hr of cohabitation with a nonestrous female. In a 3-hr preference test, males neonatally exposed to exogenous OT exhibited a significant partner preference, not seen in males receiving OTA or saline. Both OT and OTA voles had significantly higher levels of social contact than saline controls. A single neonatal injection of OT increased both total and selective social behaviors in male prairie voles.     

Oxytocin and same-sex social behavior in female meadow voles

The neuropeptide oxytocin (OT) has been implicated in a range of mammalian reproductive and social behaviors including parent-offspring bonding and partner preference formation between socially monogamous mates. Its role in mediating non-reproductive social relationships in rodents, however, remains largely unexplored. We examined whether OT facilitates same-sex social preferences between female meadow voles—a species that forms social nesting groups in short, winter-like day lengths. In contrast to results from studies of opposite-sex attachment between prairie vole mates, we found that neither OT nor dopamine neurotransmission was required for baseline levels of social partner preference formation or expression. OT enhanced preference formation beyond baseline levels—an effect that was counteracted by treatment with an oxytocin receptor antagonist (OTA). Oxytocin receptor (OTR) density correlated with social behavior in brain regions not known to be associated with opposite-sex affiliation, including the lateral septum and central amygdala. In addition, voles housed in short day lengths (SD) exhibited higher levels of OTR binding in the central amygdala, and voles exposed to high concentrations of estradiol exhibited less binding in the nucleus accumbens (NAcc) and increased binding in the ventromedial nucleus of the hypothalamus. These results suggest that same-sex social behavior shares common elements with other mammalian social behaviors affected by OT, but that the specific neural pathways through which OT exerts its influence are likely distinct from those known for sexual attachments.     

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.     

Sexual dimorphism and the NMDA receptor in alloparental behavior in juvenile prairie voles (Microtus ochrogaster)

The prairie vole (Microtus ochrogaster) exhibits parental behavior in both males and females and extensive alloparenting in juveniles. The authors studied the effects on juvenile alloparenting of antagonists for the PCP, glycine, and glutamate sites on the N-methyl-D-aspartate (NMDA) receptor. In male voles, all 3 drugs had an inverted-U dose-response curve. This change could not be attributed to fear of the pup or a nonspecific impairment of cognition, level of locomotor activity, or motor coordination. The PCP site antagonist had a U-shaped dose-response curve in females, the opposite of that in males, but neither of the other drugs changed female alloparental behavior. Both male and female voles exhibit alloparental behavior, but its neurobiological underpinnings are sexually dimorphic in juveniles.     

Males increase serum estrogen and estrogen receptor binding in brain of female voles

Sexual development of female prairie voles does not occur unless females are exposed to stimuli from an unfamiliar male. Three experiments were conducted to determine whether a saturable high-affinity estradiol binding site (ERN) is present in cell nuclei of brain tissue from females exposed to male stimuli and whether serum estradiol and brain ERN are correlated with the duration of male exposure. Brain ERN were detected and found to be correlated with serum estradiol levels. Significant increases in brain ERN were observed within 18 hours after females were exposed to a male for either a continuous (uninterrupted) or transient (1 1/4 hour) period. A significant increase in serum estradiol was observed for females given continuous male exposure. The rate of increase of ERN in brain was significantly higher for females given continuous as opposed to transient male exposure. The results suggest that the continued presence of a male can accelerate the rate of increase of ERN in the brain, presumably through increases in circulating estradiol.     

Auto- and allo-grooming in pine voles (Microtus pinetorum) and meadow voles (Microtus pennsylvanicus)

Grooming was observed in mixed-sex pairs of voles after one vole had been unilaterally soiled with a carboxymethylcellulose (CMC) gel. In Experiment 1, soiled pine voles spent more time grooming than did clean voles, and groomed the soiled side of their bodies more than the clean side. Soiled voles of both species head-groomed more than did clean voles. Addition of tastants to CMC gel did not alter grooming durations in either species, and there were no sex differences. In Experiment 2, both vole species (taken together) auto-groomed more than they allo-groomed, although clean voles groomed their soiled partners more than themselves. These studies suggest that soiled fur is a powerful stimulus for auto- and allo-grooming.     

Dopamine, oxytocin, and vasopressin receptor binding in the medial prefrontal cortex of monogamous and promiscuous voles

Comparisons between monogamous and promiscuous vole species have proven useful in examining neurobiological mechanisms underlying social attachment. Reward processing is important for social attachment, and the medial prefrontal cortex (mPFC) exerts a direct influence on reward pathways. Dopamine (DA), oxytocin (OT), and arginine vasopressin (AVP) all have been implicated in the regulation of social attachment in monogamous voles. Therefore, we used radiolabeled ligands to examine dopamine D(1)- and D(2)-like, OT, and AVP V(1a) receptor binding densities in the mPFC of monogamous and promiscuous voles. Species differences were found; monogamous voles had higher densities of D(2)-like and OT receptor binding and lower densities of D(1)-like and V(1a) receptor binding than did promiscuous voles. Sex differences also were found; females had higher densities of OT receptor binding but lower densities of V(1a) receptor binding than did males in both species. Further, the laminar distribution of receptor binding indicates the possibility of an interaction between DA and OT systems in the mPFC in the regulation of social attachment. Differences in D(1)- and D(2)-like receptor binding between species are discussed in terms of how they might modulate cortical activity and subsequent DA release in the nucleus accumbens (NAcc).     

Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster)

The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles.     

Ovarian hormones regulating sexual and social behaviors in female prairie voles, Microtus ochrogaster.

In the induced ovulator, Microtus ochrogaster (the prairie vole), daily injections of estradiol benzoate (EB 0.5 μg or 5.0 μg) facilitated high levels of sexual receptivity in ovariectomized females withing 48 hr of the onset of treatment. A lower level of EB (0.05 μg) with or without progesterone (0.5 mg) for five days did not induce lordosis. Four hr after sexually receptive EB-primed females received progesterone (0.5 mg) they either continued to show lordosis (EB 5.0 μg group) or showed an inhibition of lordosis (EB 0.5 μg group). Within 24 hr lordosis was markedly reduced in both groups. Progesterone-associated inhibitions were no longer apparent 48 hr after progesterone was discontinued. This general pattern of response to ovarian hormones is consistent with data described for other induced ovulators.     

Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles

Although oxytocin (OT) and dopamine (DA) have been implicated in pair bond formation in monogamous prairie voles (Microtus ochrogaster), the nature of potential interactions between these two neurochemical systems and the brain circuits important for such interactions in the regulation of pair bonding have not been explored. Here, we demonstrated that access to both OT and DA D2-type receptors is necessary for pair bond formation, as blockade of either type of receptor prevented partner preferences induced by OT or a D2-type agonist. We also demonstrated that the nucleus accumbens (NAcc) is a brain area important for such OT-DA interactions. In NAcc, blockade of OT receptors prevented partner preferences induced by a D2-type agonist whereas blockade of D2-type, but not D1-type, DA receptors blocked OT-induced partner preferences. Together, our data suggest that concurrent activation of OT and DA D2-type receptors in NAcc is essential for pair bond formation in female prairie voles.     

Comparisons of nipple attachment and incisor growth among four species of voles (Microtus)

Patterns of nipple attachment and incisor growth were compared between four species of voles (Microtus). Offspring of two highly social species, prairie voles (M. ochrogaster) and pine voles (M. pinetorum). were shown to cling tightly to the nipples of their dams on Days 2, 6, and 10. This pattern contrasted to weak nipple attachment displayed by two less-social species, meadow voles (M. pennsylvanicus) and montane voles (M. montanus). Lengths of the upper (maxillary) and lower (mandibular) incisors of the four species were recorded throughout the first 10 days of age and in adults. Incisors of the pine and prairie voles typically erupted earlier and grew longer than those of the meadow or montane voles during the first few days of development. Incisors grew at a substantial rate in the latter two species, such that they equalled or surpassed the incisor lengths of the former two species as Day 10 and weaning approached. Patterns of incisor growth, in part, reflected those for nipple attachment, but do not appear to account substantially for differences in nipple attachment. ©1994 John Wiley & Sons, Inc.     

Castration does not inhibit aggressive behavior in adult male prairie voles (Microtus ochrogaster)

The relationship between castration and reduced male aggression is well established. However, anecdotal observations of male prairie voles (Microtus ochrogaster) suggest that castration does not reduce aggressive behavior. To investigate the role of testicular androgens on aggressive behavior, castrated or gonadally intact male prairie voles were paired in a neutral arena with a gonadally intact vole. Castration did not reduce the frequency of intermale aggression. In Experiment 2, aggressive behavior was examined further using resident-intruder, grouped aggression, and aggression against a lactating female models. Again, castration did not affect the frequency of aggression in male prairie voles. Taken together, the results of this study suggest that aggressive behavior may be independent of gonadal steroid hormones in adult male prairie voles.