Maternal Aggression In Rats Research Articles

Sensory, hormonal, and neural basis of maternal aggression in rodents.

We review existing knowledge of the neural, hormonal, and sensory basis of maternal aggression in the female rat. Although females may express different kinds of aggression, such as defense or dominance, the most frequent and conspicuous form of aggressive behavior among females is the one associated with motherhood. Maternal aggression occurs in various vertebrate and invertebrate species; however, our emphasis will be on maternal aggression in rats because most of the physiological investigations have been performed in this species. Firstly, we address those factors that predispose the female to attack, such as the endocrine profile, the maternal state, and the stimulation provided by the pups, as well as those that trigger the aggressive response, as the intruder's characteristics and the context. As the postpartum aggression is a fundamental component of the maternal repertoire, we emphasize its association with maternal motivation and the reduction of fear and anxiety in dams. Finally, we outline the neurocircuitry involved in the control of maternal aggression, stressing the role of the ventro-orbital region of prefrontal cortex and the serotoninergic system.

Vasopressin mediates enhanced offspring protection in multiparous rats

Maternal aggression is highly expressed during lactation and serves to protect the developing young from intruders that may injure the offspring. One neurochemical modulator of maternal aggression appears to be arginine vasopressin (AVP). Earlier research supports a role for AVP in maternal aggression in rats as treatment with an AVP antagonist in lactating, primiparous rats stimulates the mother's aggression towards intruders the second half of lactation, but AVP itself was without major effects during early lactation. Recent behavioral findings indicate that during a second lactation (multiparous) mothers display higher levels of maternal aggression than do first time mothers (primiparous). The present study was designed to assess the involvement of AVP as mothers acquire reproductive experience. Therefore, the involvement of AVP in maternal aggression in multiparous mothers was measured after intracerebroventricular (ICV) treatment with both AVP and a V1a receptor antagonist. Behavior was assessed during early lactation when aggression levels are very high in multiparous mothers as well as during late lactation when aggression levels are lower. The results demonstrated that ICV infusions of AVP significantly reduced maternal aggression in multiparous females on day 5 of lactation, whereas V1a antagonist infusions increased aggression on day 15 of lactation. These findings suggest that the role of AVP in maternal aggression may be amplified as reproductive/lactational experiences increase, and support the involvement of the central AVP system as a key modulator of maternal protection of the young.

Effect of 5-HT1B receptor agonists injected into the prefrontal cortex on maternal aggression in rats

Serotonin (5-HT1B) receptors play an essential role in the inhibition of aggressive behavior in rodents. CP-94,253, a 5-HT1B receptor agonist, can reduce aggression in male mice when administered directly into the ventro-orbitofrontal (VO) prefrontal cortex (PFC). The objective of the current study was to assess the effects of two selective 5-HT1B receptor agonists (CP-94,253 and CP-93,129), microinjected into the VO PFC, on maternal aggressive behavior after social instigation in rats. CP-94,253 (0.56 microg/0.2 microL, N = 8, and 1.0 microg/0.2 microL, N = 8) or CP-93,129 (1.0 microg/0.2 microL, N = 9) was microinjected into the VO PFC of Wistar rats on the 9th day postpartum and 15 min thereafter the aggressive behavior by the resident female against a male intruder was recorded for 10 min. The frequency and duration of aggressive and non-aggressive behaviors were analyzed using ANOVA and post hoc tests. CP-93,129 significantly decreased maternal aggression. The frequency of lateral attacks, bites and pinnings was reduced compared to control, while the non-aggressive behaviors and maternal care were largely unaffected by this treatment. CP-94,253 had no significant effects on aggressive or non-aggressive behaviors when microinjected into the same area of female rats. CP-93,129, a specific 5-HT1B receptor agonist, administered into the VO PFC reduced maternal aggressive behavior, while the CP-94,253 agonist did not significantly affect this behavior after social instigation in female rats. We conclude that only the 5-HT1B receptor agonist CP-93,129 administered into the VO PFC decreased aggression in female rats postpartum after social instigation.

Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams.

Gestational cocaine treatment in rat dams results in decreased oxytocin (OT) levels, up-regulated oxytocin receptor (OTR) binding density and decreased receptor affinity in the whole amygdala, all concomitant with a significant increase in maternal aggression on postpartum day six. Rat dams with no gestational drug treatment that received an infusion of an OT antagonist directly into the central nucleus of the amygdala (CeA) exhibited similarly high levels of maternal aggression towards intruders. Additionally, studies indicate that decreased OT release from the hypothalamic division of the paraventricular nucleus (PVN) is coincident with heightened maternal aggression in rats. Thus, it appears that cocaine-induced alterations in OT system dynamics (levels, receptors, production, and/or release) may mediate heightened maternal aggression following cocaine treatment, but the exact mechanisms through which cocaine impacts the OT system have not yet been determined. Based on previous studies, we hypothesized that two likely mechanisms of cocaine's action would be, increased OTR binding specifically in the CeA, and decreased OT mRNA production in the PVN. Autoradiography and in situ hybridization assays were performed on targeted nuclei in brain regions of rat dams on postpartum day six, following gestational treatment twice daily with cocaine (15 mg/kg) or normal saline (1 ml/kg). We now report cocaine-induced reductions in OTR binding density in the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST), but not the CeA. There was no significant change in OT mRNA production in the PVN following cocaine treatment.

Dose-related effects of chronic gestational cocaine treatment on maternal aggression in rats on postpartum days 2, 3, and 5

1. Gravid Sprague-Dawley rats received subcutaneous injections of saline, 3.5, 7.5 or 15 mg/kg of cocaine, twice daily, throughout gestation. 2. On postpartum days 2, 3, and 5, dams and their litters (surrogate or natural) were videotaped for 10 minutes in the presence of a male rat for assessment of aggression towards the intruder. Oxytocin levels in discrete brain areas were assayed on postpartum day 5. 3. The 30 mg/kg dose group had a significantly greater increase in the frequency of threats from postpartum day2 through postpartum day 5 than the 7.5 mg/kg cocaine and the non-yoke-fed saline control groups. 4. Dams with natural litters exhibited a significantly greater frequency of receptive behavior compared to dams with surrogate litters. 5. There were no significant differences in oxytocin levels between the 30 mg/kg cocaine-treated group and the other treatment or control groups on postpartum day 5. 6. There are very few statistically significant cocaine-induced increases in maternal aggressive behavior and no dose-dependent decreases in amygdaloid OT levels in the early postpartum period.

Hypothalamic Paraventricular Nucleus Modulates Maternal Aggression in Rats: Effects of Ibotenic Acid Lesion and Oxytocin Antisense

GIOVENARDI, M., M. J. PADOIN, L. P. CADORE AND A. B. LUCION. Hypothalamic paraventricular nucleus modulates maternal aggression in rats: Effects of ibotenic acid lesion and oxytocin antisense. PHYSIOL BEHAV 63(3) 351–359, 1998.—Central oxytocin (OT) appears to be crucial for maternal behavior. OT, through the parvocellular neurons of the hypothalamic paraventricular nucleus (PVN), can exert its physiological and behavioral effects by acting on OT receptors in nonpituitary projections of the PVN. The purpose of the present study was to analyze the role of the PVN and OT on maternal aggressive behavior in two different periods after delivery: on the fifth day (period of high aggressiveness) and on the eighteenth day postpartum (period of low aggressiveness). In the first experiment, ibotenic acid was injected into the PVN in order to lesion the parvocellular neurons. A second experiment was designed to study more specifically the effects of OT using the antisense technique. On the fifth day postpartum, both the PVN lesion by the ibotenic acid and a possible acute reduction of OT synthesis by the antisense administration in that nucleus increased maternal aggressive behavior, while on the eighteenth day postpartum no effect was recorded. We may conclude that central projections of the PVN modulate maternal aggression during a restricted period after delivery, only when lactating females show naturally high levels of aggressive behaviors.

Hypothalamic paraventricular nucleus, oxytocin, and maternal aggression in rats.

Both the lesion of the parvocellular region of the PVN (FIG. 1) and the acute reduction of OT synthesis in that nucleus (FIG. 2) increase maternal aggression in rats. Previous work showed that ibotenic acid as well as the OT antisense in the PVN reduced the level of OT in the brainstem, but not in the pituitary. Therefore, the oxytocinergic parvocellular neurons of the PVN appear to exert an inhibitory effect on the aggressive behavior of the lactating female rat against an adult intruder. In a relationship of a different nature, mother-infant, a facilitatory effect of OT has been shown. Previous work showed a significant decrease of OT mRNA levels in the PVN of female rats during the first 10 days after delivery compared to late pregnancy, which is the inverse ratio of the natural temporal evolution of maternal aggressive behavior. Furthermore, in the present work, a functional decrease of OT mRNA was probably the effect of the antisense in the PVN. In conclusion, OT cells in the PVN appear to play different roles on maternal care and maternal aggression.

Lasion of hypothalamic paraventricular nucleus and maternal aggressive behavior in female rats

Lactating female rats on the 3rd to 12th day postpartum are more aggressive towards an intruder male than are nonlactating females. In this study, maternal aggressive behavior was recorded by introducing a strange male in the territory of the female and her offspring, on the fifth, seventh, and ninth day postpartum. Electrolytic lesions of the paraventricular nucleus of the hypothalamus (PVN) were performed on the fifth day postpartum. The results showed that the PVN lesion reduced the frequency and duration of attacks on the intruder. In addition, the lesion caused reduced weight gain in the pups compared to pups of the sham lesion group. The results suggest that PVN participates in the modulation of maternal aggression in rats. A possible role of oxytocin in that behavior is discussed.

On the dual nature of maternal aggression in rats

Presentation of a natural predator, a cat, was used to differentiate elements of maternal attack by female rats on a male intruder. Following exposure (without direct physical contact) of post-partum females to a cat or to a toy stuffed cat (control group), the females were replaced in their home cages and presented with a male intruder rat. Cat exposure reliably decreased lateral attack to the intruder, as well as locomotion, but had no effect on either jump attack or an upright defensive posture (boxing). Since predator exposure produces a somewhat durable increase in defense, along with inhibition of nondefensive behavior, these results suggest that maternal aggression represents a mixture of offensive, usually related to competition, and defensive (protective) behaviors. The results indicate that maternal aggression, as a parental care behavior, appears to be at least partially resistant to fear. © 1996 Wiley-Liss, Inc.

On the dual nature of maternal aggression in rats

Presentation of a natural predator, a cat, was used to differentiate elements of maternal attack by female rats on a male intruder. Following exposure (without direct physical contact) of post-partum females to a cat or to a toy stuffed cat (control group), the females were replaced in their home cages and presented with a male intruder rat. Cat exposure reliably decreased lateral attack to the intruder, as well as locomotion, but had no effect on either jump attack or an upright defensive posture (boxing). Since predator exposure produces a somewhat durable increase in defense, along with inhibition of nondefensive behavior, these results suggest that maternal aggression represents a mixture of offensive, usually related to competition, and defensive (protective) behaviors. The results indicate that maternal aggression, as a parental care behavior, appears to be at least partially resistant to fear. © 1996 Wiley-Liss, Inc.

A guide to the literature on aggressive behavior

A guide to the literature on aggressive behavior

Maternal Aggression in Rats: Effects of Olfactory Bulbectomy, ZnSO4-Induced Anosmia, and Vomeronasal Organ Removal

Previous studies from our laboratory indicate that somatosensory inputs to the snout and ventral trunk, but not visual or auditory stimuli, play critical roles in the elicitation and maintenance of maternal aggression by lactating Norway rats toward a strange male intruder. There are conflicting reports on the influence of olfaction on maternal aggression. We explored the possible roles of central or peripheral anosmia on maternal aggression in Long–Evans rats during early lactation. In Experiment 1, responsiveness to both volatile and non-volatile odors was eliminated by bilateral olfactory bulbectomy (BOB), carried out during mid-gestation. BOB resulted in a reduced likelihood and intensity of maternal aggression on days 1 and 5 of lactation (L1 and L5), but also severe deficiencies in maternal behavior and litter growth and survival. In Experiment 2, anosmia to volatile odors was induced by spraying zinc sulfate intranasally on gestation day 21 and L1. This treatment had little or no effect on maternal aggression on L1 or L2 or on maternal behavior, especially if there was a 1-day recovery between the second treatment and testing. In Experiment 3, responsiveness to non-volatile odors was eliminated by vomeronasal-organ removal (VNX) carried out prior to mating. VNX did not disturb maternal behavior on L2–L8 or maternal aggression on L1 or L5. These results and others suggest that the expression of maternal aggression is affected by volatile odors, mediated possibly by accessory chemosensory systems such as the septal organ, or by neural changes that follow olfactory deafferentation, or both.

Maternal aggression in rats: Effects of visual or auditory deprivation of the mother and dyadic pattern of ultrasnic vocalizations

Previous studies indicate that somatosensory inputs to the snout and the ventral trunk play critical roles in the elicitation and maintenance of maternal aggression by postpartum lactating Long-Evans Norway rats toward a strange male intruder. In the present studies we examined the possible influence of visual and auditory stimuli in the display of this behavior. In Experiment 1, dams temporarily deprived of visual or auditory input by eyelid suturing or ear molds, respectively, on Day 2 postpartum, were found to have normal levels of maternal aggression 1 day later. In Experiment 2, males were found to contribute about 50% of the short-duration 50-kHz vocalizations, which begin shortly after introduction of the intruder, and all of the long-duration 22-kHz vocalizations, which begin after the onset of attacks. Nonetheless, females tested with males surgically devocalized 7 days earlier were not significantly different in aggressiveness from dams tested with vocalizing males on either Day 1 or Day 4 postpartum. These findings indicate that visual or auditory inputs from the pups or intruder are not critical to the display of maternal aggression in rats, at least within the confines of laboratory housing.

Quantitative and comparative analyses of pro-aggressive actions of benzodiazepines in maternal aggression of rats

The pro-aggressive effects of low doses of benzodiazepines on maternal aggression in rats were studied. Chlordiazepoxide, diazepam, oxazepam and alprazolam produced bell-shaped dose-response curves, with increased aggression at low doses. Only alprazolam significantly reduced aggression at higher doses. A comparison of the drug effects on different aggressive elements revealed that chlordiazepoxide and oxazepam increased the frequency of more elements of the aggressive repertoire than diazepam or alprazolam. Thus, although all benzodiazepine receptor agonists increased aggression, there were significant quantitative differences in their effects.

Effect of opiate receptor agonists and antagonists on maternal aggression in rats

The behavioral effects of opiate agonists and antagonists were studied on the female aggression model. Mu-agonist buprenorphine more selectively decreased maternal aggression than kappa-agonist tifluadom. Kappa-agonists (bremazocine, tifluadom) increased passive defence in lactating female rats. Ethopharmacological data shows predominant involvement of brain mu-opiate receptor system in the integrative processes of maternal behavior and maternal aggression in particular.

Medial hypothalamic involvement in maternal aggression of rats.

Extensive electrolytic lesions of the medial hypothalamus, or more restricted ones in its ventral division, decreased maternal aggression in rats operated upon on postpartum Days 2 and 3 and tested with female intruders 4 days later. Maternal aggression was attenuated also in mothers receiving intrahypothalamic infusions with ibotenic acid or parasagittal knife cuts along the lateral border of the ventromedial hypothalamic nucleus; in addition, the females with ibotenate lesions or knife cuts showed impaired lordosis behavior. None of the hypothalamic interventions were associated with deficits in pup retrieval. Lactation was impaired in groups with hypothalamic electrocoagulations but not in mothers with ibotenate lesions or knife cuts. The results suggest that the ventromedial hypothalamus and its lateral connections participate in control of maternal aggression.

The effect of pup presence and intruder behavior on maternal aggression in rats

Maternal aggression was not affected by a brief (1 min) interval of pup separation and was not dependent upon the behavior of male intruders. Dams’ latency to attack increased significantly within 4 h of pup removal. Duration of offense was decreased by 8 h of separation and all aggression was abolished after 24 h of separation. The results demonstrate that the short-term maintenance of maternal aggression does not depend on pup stimulation or the behavior of male intruders. Maternal aggression decreases systematically, however, when pups are absent for longer intervals.

Maternal aggression in rats: Changes over pregnancy and lactation in a sprague-dawley strain

Maternal aggression in a Sprague-Dawley strain of laboratory rat (Charles River CD) was explored from Day 1 after mating on Day 0 through Day 24 of lactation (L0-L24). Aggression toward unfamiliar male “intruders” during 10-min tests was low among nonpregnant, nonlactating females and during the first 10 days of gestation. Frequency of attack on intruders increased moderately but significantly by Gestation Day 16 (G16; Experiment 1) or G21 (Experiment 2), a prepartum phenomenon not previously reported in laboratory rats. Levels of aggression were highest, however, during the first 9 days of lactation, when attacks averaged more than 6 per 10-min session. Attacks declined sharply in frequency after L14 and by L24 did not exceed levels observed among nonpregnant females. Experiment 3 examined the importance of the test site (home cage with nest and pups, if any, vs unfamiliar cage without nest or pups) to agonistic behavior associated with pregnancy and lactation. Late pregnant females tested in a novel cage were not aggressive; however, females tested shortly after delivering their pups were highly aggressive, averaging over four attacks per 5-min session. In novel cage tests frequency of attack remained high through L4 but declined significantly by L7. These data are consistent with the hypothesis that maternal aggression at its onset is primarily under hormonal control, but becomes increasingly dependent upon external factors, presumably pup stimulation, during the postpartum period.

Modulatory actions of benzodiazepine receptor ligands on agonistic behaviour

Several experiments were conducted to establish the role of benzodiazepine (BDZ) receptor ligands in aggressive behaviour in male and female rats. In particular, the pro-aggressive effects of BDZ agonists was subject of investigation. Predatory aggression (mouse killing) was facilitated by chlordiazepoxide (CDP) when tested in naive female rats, but CDP was unable to induce muricide in non-killing rats with extensive experience with mice. In experiments on maternal aggression in rats a post-hoc analysis revealed that the pro-aggressive action of CDP on maternal aggression was base line dependent: the increase in aggression in spontaneously low aggressive females was significantly higher than in females with a higher base line level. A further study aimed at unravelling the underlying factors contributing to this pro-aggressive action by determining the role of opponent size on the effects induced by CDP. Normally large opponents evoke less aggression from lactating females than smaller opponents and CDP exerted its pro-aggressive effect particularly strongly in the ‘large opponent’ situation. An ethological analysis was made of lateral display—an ambivalent posture frequently occurring in agonistic behaviour—to establish whether CDP indirectly increases aggression by reducing fear by means of its anxiolytic properties. The data partly support this hypothesis. These findings stress the importance of environmental and experiential factors in the possible outcome of CDP effects on aggression. Moreover, they point to possible explanations of seemingly contradictory data. In two final experiments an inverse benzodiazepine receptor agonist (β-CCE) was tested in maternal aggression. β-CCE reduced aggression, although not in a completely specific way. A neutral BDZ-receptor antagonist (Ro 15-1788) was tried in an attempt to antagonize the pro-aggressive effects of CDP in maternal aggression. Ro 15-1788 did not counteract the pro-aggressive action of CDP, but antagonized CDP effects on exploration. The modulatory role of the benzodiazepine receptor complex in aggression remains an intriguing area of research in which many subtleties in testing conditions play a role and in which more BDZ agonists, inverse agonists and antagonists have to be tested.

Maternal aggression in rats: lack of interaction between chlordiazepoxide and fluprazine.

In a paradigm of female aggression, maternal aggression, low doses of chlordiazepoxide (CDP) enhanced aggression, whereas the serenic drug fluprazine dose-dependently decreased aggression. In this study one selected dose of CDP (5 mg/kg PO) clearly enhanced aggression of female lactating rats against a naive male intruder. This dose of CDP however, was not able to antagonize the dose-dependent decrease observed after fluprazine treatment (5, 10, 20 mg/kg IP). These data suggest that fluprazine and CDP do not simply have opposite effects at the same site of action. It is suggested that fluprazine decreased the offensive motivation of animals, whereas CDP increased attacks indirectly by reduction of the approach-avoidance conflict in a social context.