Mammary stimulation and maternal aggression in rodents: thelectomy fails to reduce pre- or postpartum aggression in rats

In mice, tactile stimulation of the nipples appears to be critical for the onset of postpartum maternal aggression. Surgical removal of the nipples (thelectomy) blocks aggression if performed prior to parturition. In rats, indirect evidence suggests a similar role for nipple stimulation in maternal aggression. Two experiments were undertaken to determine whether thelectomy prior to mating reduces pregnancy-induced and/or postpartum aggression in this species. In the first, thelectomized and sham-thelectomized females were subjected to home cage tests (pups, if any, present) with unfamiliar male intruders on Gestation Days 18 and 21 and Lactation Days 3 and 5. Additional groups of thelectomized females were tested one time only on either Lactation Day 5 or 12. Thelectomized and control females were equally aggressive; postpartum, nearly all females in both groups attacked. Experiment 2 used females that were hysterectomized-ovariectomized (HO) on Gestation Day 16. Such females are not aggressive prior to initiating maternal behavior, but become highly aggressive (over 80% attacking) after commencing maternal care. Females again were thelectomized or sham-thelectomized prior to mating. On Day 16 HO was performed, and 48 hr later continuous exposure to pups was begun. After the females had displayed maternal behavior for 1.5-2 days, intruder tests were conducted. All females attacked at least once, with no differences between treatment groups. Thus thelectomy does not reduce maternal aggression in the rat. This finding, however, does not preclude a role for tactile ventral stimulation in mediating maternal aggression.     

Postpartum aggression in mice: Experiential and environmental factors

Six experiments were conducted to assess the influence of duration of lactation, the presence of young, and the stimulus characteristics of intruder animals upon postpartum aggression of mice. The first experiment showed that postpartum aggression toward conspecifics was highest between Day 3 and Day 8, declined between Day 9 and Day 14, and was present toward males but absent toward females between Day 15 and Day 21 of the lactation period. Experiment 2 showed that lactating mice rarely attacked conspecifics to which they had been previously exposed but would readily attack strangers. Experiment 3 and 4 demonstrated that lactating animals never attacked intruders when tested 5 hr after pup removal. However, placement of young behind a wire partition in the home-cage for 5 hr or replacement of the offspring for as little as 5 min following 5 hr of separation restored postpartum aggression. The fifth experiment showed that 1- and 10-day old intruders were seldom attacked while intense aggression was directed against 14- and 20-day old intruders. Finally, Experiment 6 demonstrated that 14-day old intruders whose hair was removed were rarely attacked.     

Postpartum,hormonal, and nonhormonal induction of maternal behavior in rats: Effects on T-maze retrieval of pups

It is known that the home-cage maternal behavior of rats which become maternal after daily pup exposure (sensitization) is almost indistinguishable from that of lactating mothers, but that sensitized and lactating rats can be distinguished by their pup-retrieval performance in a T-maze extension of the home cage. The present study explored this difference further. Postpartum mothers which could not suckle due to prior nipple removal (thelectomy) retrieved as well, if not better, than intact controls in the T-maze. Hormonal induction of maternal behavior (in ? 3 days) was carried out by hysterectomy-ovariectomy plus 100 μg/kg estradiol benzoate; the performance of these females was similar to that of the postpartum groups. In contrast, only a small percentage of the sensitized mothers retrieved in the T-maze, whether the latency to onset of their maternal behavior was long (4–10 days) or short (? 3 days). Thus, hormonal factors associated with pregnancy and/or parturition, but not suckling stimulation, may facilitate T-maze retrieval of pups. The possible ethological significance of the T-maze test as a measure of maternal responsiveness is discussed.     

Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.     

Suckling behavior and its development in two Yangtze finless porpoise calves in captivity

We focally observed the suckling behavior of two Yangtze finless porpoise calves, C05 and C07, in captivity. Between 15 and 730 days postpartum of C05 and between birth and 30 days postpartum of C07, 286.3 (1.9 ± 0.4 hr/day (mean ± standard deviation), n = 148 days) and 18.3 hr (2.0 ± 0.5 hr/day, n = 9 days) of video footage were recorded, in which 429 and 111 suckling events were observed, respectively. We found that the calves made their initial suckling attempts after repeated stroking of the mother's body with their rostrums. The suckling duration was 4.4 ± 1.8 sec and 4.8 ± 2.4 sec, respectively. Before suckling, the calves swam under the mother's genital region (99.1% of number of event, respectively). During suckling, the mother generally turned sideways to facilitate the calves' suckling (80.7 and 76.6%, respectively). The calves almost equally used the two mammary slits [52.2% (left) and 47.8% (right), and 44.1% (left) and 55.9% (right), respectively]. The frequency and proportion of time C05 spent suckling continuously decreased to zero by 483 days postpartum. The two variables for C07 increased following birth, to a peak at 16 days postpartum, and then decreased continuously until 30 days postpartum. We discuss the possible implications of these observations for the management and conservation of this endangered cetacean.     

Effect of the D1-receptor antagonist SCH-23390 on the individual and aggressive behavior in male mice with various aggression experience

It has been shown that dopaminergic systems are involved in mechanisms of aggressive behavior. Effects of SCH 23390 (dopamine Di receptors antagonist. 0-1 mg/kg, i/p, 30 min) on aggressive and individual behaviors were studied in male C57BL/6J mice with different experience of aggression. SCH 23390 reduced aggressive attacks in animals without preliminary experience of aggression. However total time of hostile behavior (sum of the total time of attacks, aggressive grooming and diggings) didn't changed. No significant effects on behaviors were found in mice with long (20 days) repeated experience of aggression. It was supposed that long aggressive experience produces pharmacological desensitization of Di receptors as a result of enhanced dopaminergic activity shown earlier in aggressive animals.     

Effects of ergocornine and prolactin on aggression in the postpartum golden hamster

The effects on aggressive behavior of prolactin (PRL) and ergocornine hydrogen maleate, an inhibitor of PRL secretion, were investigated in the female golden hamster. Because high aggression and PRL levels are associated with lactation in hamsters, postpartum females were used as subjects. In the first experiment, three groups of ovariectomized and hysterectomized females were compared: normally lactating, ergocornine-treated, and ergocornine plus replacement PRL treated. Normally lactating mothers were typically aggressive towards males in an arena, whereas females given ergocornine were not. Females given both ergocornine and PRL showed an intermediate level of aggression. Although ergocornine suppressed aggression towards adult males, attacks on pups increased. A second experiment sought to determine if ergocornine would depress aggression when PRL involvement was unlikely. At least 30 days following pup removal, females from the first experiment were “trained” to attack home-cage intruders consistently. After ergocornine administration, home-cage attacks by these experienced females were not diminished. Since PRL levels were probably low in these animals, it was concluded that the effects of ergocornine on aggression were limited to instances in which PRL was involved, and that PRL probably can facilitate aggression.     

Upregulation of astrocytic basic fibroblast growth factor in the cingulate cortex of lactating rats: time course and role of suckling stimulation

Previous work from our laboratory has shown that there is a much higher level of bFGF and GFAP immunoreactivity in area 2 of the cingulate cortex (Cg2) of rats on day 16 of lactation than in cycling or late pregnant females. To examine the time course of this change, in the first of the current studies, we compared bFGF and GFAP immunoreactivity in the brains of lactating females on postpartum day 4 (PP4), day 10 (PP10), day 16 (PP16), and day 24 (PP24) with that of cycling and ovariectomized (OVX) females. In the second study, we investigated whether the maintenance of these changes in bFGF and GFAP depended on suckling stimulation by removing litters on day 1 or day 16 postpartum and examining the brains of the dams on day 4 (Pr4) or day 24 (Pr24) postpartum, respectively. bFGF and GFAP immunoreactivity within Cg2 and the medial preoptic area (MPOA) were measured. In both experiments astrocytic bFGF and GFAP surface density in the Cg2 varied significantly across groups. All postpartum rats, regardless of stage of lactation or presence of the litter, had significantly higher levels of bFGF and GFAP immunoreactivity than cycling animals. Thus, the maintenance of this upregulation in bFGF and GFAP immunoreactivity does not depend on suckling stimulation. Consistent with our previous report, astrocytic bFGF was also elevated in the MPOA of PP16 animals. These data suggest a robust, long-lasting, postpartum change in bFGF and GFAP immunoreactivity in Cg2 and a role for this area of the cortex in the physiological and behavioral adaptations that accompany reproductive experience.     

Mice: postpartum aggression is elevated following prenatal progesterone exposure

Pregnant Rockland-Swiss (R-S) mice were injected with sesame oil or 250 or 500 micrograms of progesterone (P) on Days 12 through 16 of gestation and the postpartum aggressive behavior of their female offspring was examined in adulthood. Both doses of P significantly increased the intensity of aggression (number of attacks) exhibited by the female offspring toward an adult male intruder. The low dose of P also produced significant increases in relative anogenital distance. These effects were seen in the absence of any effects on body weight at birth or in adulthood, or on reproductive performance. The findings support previous research, in both animals and humans, showing that prenatal brain differentiation and subsequent behavior are masculinized by prenatal exposure to progesterone.     

The relationship between different types of genetically defined aggressive behavior

Aggressive behavior is not a unitary trait, and different stimuli/situations elicit different kinds of aggressive behavior. According to numerous data the genotype plays a significant role in the expression of aggressive behavior. However, it remains unclear how genetic predisposition to one kind of aggression is linked with other kinds of aggressive behavior, especially pathological aggression (infanticide). Here, we report on our investigation of the expression of defensive, offensive, predatory and asocial aggression in wild rats selectively bred for 85 generations for either a high level or a lack of aggression towards humans. We found that those rats genetically predisposed to a high level of defensive aggression showed decreased social behavior and increased pathological aggressive behavior towards juvenile males. The highly aggressive rates showed a reduced latency time of attack and an increased latency time of the first social contact. Rats genetically predisposed to defensive aggression demonstrated increased predatory aggression—latency time of muricide was shorter in highly aggressive than in tame animals. At the same time, both lines of rats did not differ significantly in intermale aggression. We conclude that the data indicate a close relation between defensive, predatory and pathological aggressive behavior that allows us to suggest that similar genetic mechanisms underlie these types of aggressive behavior.     

Developmental changes in rat thyroid responsiveness to thyrotropin administered by the subcutaneous and peroral route

It has been demonstrated that orally administered thyrotropin (bovine, bTSH) evokes an increase in circulating T4 and T3 levels in 15-day-old suckling rat pups, but not in weaned animals. Because the feedback mechanisms of the hypothalamo-pituitary-thyroid axis change dramatically during the neonatal period, we chose to examine the efficacy of exogenous bTSH in eliciting a thyrostimulatory response via the subcutaneous (sc) or peroral (po) route in rat pups at 5, 8, 12, and 15 days postpartum. Suckling pups were divided into four groups and received one of the following: (i) 2 IU bTSH/100 g body wt administered sc; (ii) distilled H2O (dH2O) sc; (iii) 2 IU bTSH/100 g body wt given po; (iv) dH2O po. Animals were sacrificed at Time 0 and 1, 2, and 3 hr post-treatment, and the collected serum was analyzed for T4 and T3 by RIA. Maximum serum T4 levels were attained at 2-3 hr post-treatment, and the T4 response to sc-bTSH was significantly greater than that of the po-bTSH groups at all ages examined. This difference became progressively greater with increasing age, due to a persistent decline in T4 responsiveness in animals receiving po-bTSH. No significant differences in T4 or T3 levels attained were observed in 8-day-old rat pups treated with rat vs bovine TSH, either sc or po. Percentage T4 response (vs basal levels) steadily declined between Days 5 and 15 postpartum, in both sc- and po-bTSH treatment groups. Percentage T3 responsiveness to sc-bTSH also declined between 5 and 12 days postpartum, after which time T3 generation increased. Our results suggest that the neonatal rat is highly responsive to exogenous TSH late in the first week of life, and that the permeability of the gut at this stage of development further facilitates the impact of orally ingested TSH in the suckling.     

Paternal aggression in a biparental mouse: parallels with maternal aggression

Environmental and social factors have important effects on aggressive behaviors. We examined the effect of reproductive experience on aggression in a biparental species of mouse, Peromyscus californicus. Estrogens are important in mediating aggressive behavior so we also examined estrogen receptor expression and c-fos for insights into possible mechanisms of regulation. Parental males were significantly more aggressive than virgin males, but no significant differences in estrogen receptor alpha or beta expression were detected. Patterns of c-fos following aggression tests suggested possible parallels with maternal aggression. Parental males had more c-fos positive cells in the medial amygdala, and medial preoptic area relative to virgin males. The medial preoptic area is generally considered to be relatively less important for male-male aggression in rodents, but is known to have increased activity in the context of maternal aggression. We also demonstrated through habituation-dishabituation tests that parental males show exaggerated investigation responses to chemical cues from a male intruder, suggesting that heightened sensory responses may contribute to increased parental aggression. These data suggest that, in biparental species, reproductive experience leads to the onset of paternal aggression that may be analogous to maternal aggression.     

Interaction effects of corticosterone and experience on aggressive behavior in the green anole lizard

Aggressive encounters are accompanied by a release of stress hormone, and this corticosterone (CORT) secretion could influence aggressive behavior in subsequent encounters. We investigated the modulating effects of CORT on aggressive behavior in the context of a 5-day social experience in male green anole lizards. In Experiment 1, we measured plasma CORT levels in animals that were exposed for different times to aggressive males. In Experiment 2, using metyrapone, a CORT synthesis blocker, we tested whether CORT secretion in response to the aggressive stimulus plays a role in experience-dependent facilitation of aggressive behavior. We hypothesized that aggressive encounters would increase plasma CORT levels, and that blocking CORT synthesis with metyrapone treatment during the aggressive encounter would cause an animal to become more aggressive. We also tested whether blocking CORT would interfere with the influence of 5-day social experience on animals' behavior in a subsequent aggressive encounter. Animals that were exposed to another male showed higher plasma CORT levels immediately after the 10 min encounter than animals exposed to the non-social video, and this high level was maintained through day 5. Within the aggressive video groups, in Experiment 2, there was a distinctly different pattern in displays depending on drug condition: vehicle-injected animals showed gradual increases followed by decreases in aggressive behavioral responses to the video as the five days proceeded (habituation), while animals injected with metyrapone started out with high aggressive behavior and did not decrease behavioral responses at later trials (no habituation). Finally, when tested with a novel conspecific on day 6, animals previously injected with metyrapone showed no higher aggression than did animals previously injected with vehicle and exposed to the aggressive video. These results suggest that blocking CORT synthesis during the exposure to the aggressive video induced animals to remain aggressive toward the repetitive stimulus without habituating, while not becoming more aggressive than controls toward a novel challenger.     

Female marmosets' behavioral and hormonal responses to unfamiliar intruders

The endocrine control mechanisms for female mammalian aggression have been largely unstudied. Although it has been proposed that androgens may modulate female aggressive behavior in a similar manner to males, very little conclusive evidence exists. Previous work in male marmosets found that post‐encounter increases in testosterone (T) were dependent on the intensity of aggression displayed during the aggressive encounter. We exposed female marmosets (Callithrix kuhlii), a monogamous and biparental primate, to aggressive interactions with unfamiliar intruders. Individual female marmosets exhibited changes in T and estradiol (E₂) that are associated with aggressiveness dependent on the intensity of aggression displayed as well as their role during the encounter. Resident females exhibited increased E₂ immediately following an encounter in which they displayed high rates of aggression. If resident females received high rates of aggression from the intruder, the resident displayed increased T 24 hr following the encounter. Interestingly, if the female was an intruder in the encounter, the intensity of her aggression was associated with increased cortisol immediately following the trials, whereas received aggression was associated with increased T and E₂ immediately following the trial. Female primates do exhibit situation‐dependent changes in gonadal steroids in association with aggression that may serve to prime them for future aggressive interactions. Am. J. Primatol. 73:1072–1081, 2011. © 2011 Wiley‐Liss, Inc.     

The Effects of Social Experience on Aggressive Behavior in the Green Anole Lizard (Anolis carolinensis)

To understand how context-specific aggression emerges from past experience, we examined how consecutive aggressive encounters influence aggressive behavior and stress responses of male green anole lizards ( Anolis carolinensis ). Animals were shown a video clip featuring an aggressively displaying conspecific male, which provoked aggressive responding, while control animals viewed a neutral video. After 5 d of interaction with the videos, both the subject and control groups were presented with a live conspecific. As a non-invasive assay of stress responses, we measured changes in body color and eyespot darkness, two features known to be strongly correlated with titers of stress hormones. Our results demonstrate that experience increased aggression in male anoles, but that increases in aggression to a repeated stimulus were transient. Tests with a novel conspecific indicate that the experienced animals remained aggressive when presented with novel stimuli. Although there were differences in the morphological indicators of the stress response between experimental and control groups during video presentations, there were no differences when presented with novel conspecifics. These data indicate that experience-dependent differences were not mediated by differences in the 'stressfulness' of aggressive interaction, as thought to be the case for animals in chronic subordinate/dominant dyads. We suggest that habituation and reinforcement interact to promote aggressive responding and to restrict it to novel individuals. Such context specificity is a hallmark of natural patterns of aggression in territorial species.     

Opposing hormonal mechanisms of aggression revealed through short-lived testosterone manipulations and multiple winning experiences

Territorial aggression is influenced by many social and environmental factors. Since aggression is a costly behavior, individuals should account for multiple factors such as population density or reproductive status before engaging in aggression. Previous work has shown that male California mice (Peromyscus californicus) respond to winning aggressive encounters by initiating aggression more quickly in future encounters, and we investigated the physiological basis for this effect. We found that injections that produced a transient increase in testosterone (T) following an aggressive encounter caused males to behave more aggressively in an encounter the following day. Experience alone was not enough to change aggression, as males treated with saline injections showed no change in aggression. The effect of T injections on aggression was androgen-based, as the inhibition of aromatase did not block the T injections from increasing aggression. Aromatase inhibition did, however, increase aggression in the initial aggression tests (before application of T or saline injections), and aromatase activity in the bed nucleus of the stria terminalis (BNST) was negatively correlated with aggression. A previous study suggested that aromatase activity in the BNST decreases after males become fathers. Thus, distinct neuroendocrine mechanisms allow male California mice to adjust aggressive behavior in response to changes in social and reproductive status.     

The role of progesterone in pregnancy-induced aggression in mice

A series of six experiments was performed in order to explore the potential involvement of progesterone (P) in pregnancy-induced aggression (PIA) displayed by Rockland-Swiss mice toward adult male intruders. In Experiment 1, circulating levels of P and aggression were low on gestation Days 6 and 10 while both the behavior and the steroid reached peak levels by gestation Day 14. By gestation Day 18 (the day prior to parturition), serum P was at its lowest level yet aggressive behavior was still intense. Also, individual differences in the display of fighting behavior by pregnant females were not related to circulating P. Experiments 2 and 3 showed that supplemental P treatment to early pregnant female mice did not advance the onset of aggression. Experiment 4 showed that P treatment promoted the onset and elevated the incidence of aggression in virgin mice, but only in those females with intact ovaries. Experiment 5 showed that the aggressive behavior of P-stimulated virgin females was qualitatively and quantitatively different from that exhibited by pregnant mice in that the former exhibited fewer attacks and lunges than the latter. Finally, Experiment 6 showed that the removal of P from aggressive, P-stimulated virgins dramatically attenuated levels of the behavior. This contrasts sharply with the continued fighting behavior observed in late pregnant P-deficient mice. Thus, although P augments aggression in female mice it apparently is not a sufficient stimulus for producing pregnancy-like aggressive behavior.     

The estrogenic arousal of aggressive behavior in female mice

Experiments were conducted to determine the conditions under which estrogen would promote male-like aggressive behavior in female mice. The results of the first experiment showed that most females chronically exposed to testosterone propionate (TP) in adulthood fought, whereas females similarly treated with estradiol benzoate (EB) did not display aggression. Another experiment found that, when either TP or EB was administered on the day of birth, adult females displayed aggression in response to daily EB injections during adult life. Also, the potentiating effect of neonatal hormone exposure declined over the first 12 days postpartum, as 100% of the Day 0, 75% of the Day 6, and 0% of the Day 12 and 18 TP-treated females fought in response to daily injections of 40 μg of EB in adulthood. The final study showed that, under the test conditions employed, the failure of a chronic adult EB regimen to promote aggression was not due to a competing tendency to display female sexual behavior.     

Impaired social recognition in male mice with repeated experience of aggression

Social recognition is crucial for many aspects of animal behavior in stabilized population. Preliminary data proposed impairment of social recognition in male mice with long experience of aggression. To check this hypothesis, experiments with male mice with different aggressive experience (during 2 and 20 days) were performed. Two types of losers were used as partners: losers with active defense reactions and losers displaying submissive postures. The enhanced aggressive motivation was found in both groups of aggressors. Mice with short aggressive experience demonstrated intensive attacks toward the active losers and decreased aggression directed to submissive losers. Mice with long aggressive experience did not change their behavior depending on a type of the partner and displayed a high level of aggression as a result of dominant aggressive motivation and impaired social recognition.     

Acute effect of suckling on gonadotropin, prolactin and glucocorticoid concentrations in serum of intact and ovariectomized beef cows

Suckling may prolong the anovulatory period postpartum by 1) a neural-mediated inhibition of luteinizing hormone-releasing hormone (LHRH)-induced gonadotropin secretion, or 2) an inhibitory effect of hormones released by suckling on gonadotropin secretion and/or action at the ovary. In the present investigation we considered whether a suckling event caused 1) acute inhibition of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, and 2) release of glucocorticoids and/or prolactin (PRL). Six Hereford cows remained intact and six were ovariectomized (ovx) on day 7 postpartum. Calves remained with their dams continuously. Cows were bled at 10-min intervals during 6 consecutive hr on days 14, 28 and 42 postpartum. Both LH and FSH were released episodically by day 14 in intact and ovx cows, but suckling did not acutely affect LH and FSH secretion. A PRL release accompanied suckling 67, 96 and 95% of the time. However, among all instances where PRL was released on days 14, 28 and 42 postpartum, 67, 29 and 37% occurred independent of a suckling event. Glucocorticoids were not released by suckling in intact cows but were released in ovx cows. We conclude that suckling does not acutely affect LH or FSH concentrations in serum of cows postpartum, that PRL concentrations usually increase in serum coincident with suckling but can be released at other times, and suckling-induced glucocorticoid release depends upon the presence of the ovary.