Annabel Ferreira

Role of maternal behavior on aggression, fear and anxiety.

Concomitant to the expression of maternal behavior, the lactating female develops anxiolysis in the elevated plus maze test, aggression towards intruders and reduced fear in response to a sudden auditory stimulus. This study aims to determine if these behavioral changes are associated with maternal behavior independently of the endocrine status that characterizes gestation, parturition and lactation. To assess this purpose, the behavior of lactating females was compared to that exhibited by maternal and nonmaternal ovariectomized rats untreated with steroid hormones. In contrast with lactating dams, sensitized animals (rats that displayed maternal behavior after a continuous contact with young pups) did not display reduced anxiety in the plus maze test. However, the sensitized females showed behaviors characteristic of lactating rats, such as some components of maternal aggression and reduced fear, though much less intensely than dams. These results suggest that aggression and reduced fear, but not anxiolysis, partially depend on the development of maternal behavior.

Experimental anxiety in the black and white model in cycling, pregnant and lactating rats

This study demonstrates changes in experimental anxiety assessed in the black and white paradigm during various reproductive states of female rats. Low levels of experimental anxiety were observed during late proestrus and on day 17 of gestation, stages related to high progesterone (P) levels. In estrus, metestrus, diestrus and on day 21 of gestation, stages characterized by low P concentrations, high levels of experimental anxiety, similar to those exhibited by ovariectomized females, were found. No changes in experimental anxiety were observed on day 8 of lactation compared to ovariectomized females. These data are discussed from the standpoint of the putative anxiolytic-like effect of progestins.

Demanding pups improve maternal behavioral impairments in sensitized and haloperidol-treated lactating female rats

The impairments in the maternal behavior of ovariectomized sensitized females, relative to lactating dams, resemble those deficits found in lactating females after treatment with the D1/D2 DA receptor antagonist haloperidol, which interferes with maternal motivation. Therefore, it could be speculated that these behavioral deficits found in sensitized females and haloperidol-treated dams are due to a reduced motivation to interact with pups. In support of this hypothesis, we have found that both sensitized and haloperidol-treated lactating females exhibited remarkably similar impairments in the expression of all active maternal behaviors relative to lactating dams. Furthermore, these deficits were overridden when they were allowed to interact with 12h-isolated pups (demanding pups). Interestingly, lactating dams also improved their maternal behavior in the presence of demanding pups, and clearly chose demanding more than non-demanding pups in a preference paradigm. These data support the idea that the behavioral deficits of sensitized and haloperidol-treated lactating females are due to a reduced behavioral activation in response to the incentive cues from pups compared to lactating dams, and not because of a motor inability to express maternal behavior. These findings ultimately suggest that pups modulate the activity of DA system involved in the regulation of maternal behavior.

Flexibility and adaptation of the neural substrate that supports maternal behavior in mammals

Maternal behavior is species-specific and expressed under different physiological conditions, and contexts. It is the result of neural processes that support different forms (e.g. postpartum, cycling sensitized and spontaneous maternal behavior) and modalities of mother-offspring interaction (e.g. maternal interaction with altricial/precocious young; selective/non-selective bond). To understand how the brain adapts to and regulates maternal behavior in different species, and physiological and social conditions we propose new neural models to explain different forms of maternal expression (e.g. sensitized and spontaneous maternal behavior) and the behavioral changes that occur across the postpartum period. We emphasize the changing role of the medial preoptic area in the neural circuitry that supports maternal behavior and the cortical regulation and adjustment of ongoing behavioral performance. Finally, we discuss how our accumulated knowledge about the psychobiology of mothering in animal models supports the validity of animal studies to guide our understanding of human mothering and to improve human welfare and health.

New theoretical and experimental approaches on maternal motivation in mammals.

Maternal behavior is expressed in different modalities, physiological conditions, and contexts. It is the result of a highly motivated brain, that allows the female to flexibily adapt her caring activities to different situations and social demands. To understand how mothers coordinate maternal and other motivated behaviors we discuss the limitations of current theoretical approaches to study maternal motivation (e.g. distinction between appetitive and consummatory behaviors), and propose a different approach (i.e. motorically active vs. passive motivations) and a distinction between maternal motivated state and maternal motivated behaviors. We review the evidence supporting dopamine mediation of maternal motivation and describe how different phases of the dopaminergic response - basal, tonic, and phasic release in the nucleus accumbens - relate to increased salience, invigorating behavior, and behavioral switching. The existing and new experimental paradigms to investigate maternal motivation, and its coexpression and coordination with other social or non-social motivations are also analyzed. An example of how specificity of motivational systems (e.g. maternal and sexual behavior at postpartum estrus) could be processed at the neural level is also provided. This revision offers new theoretical and experimental approaches to address the fundamental question of how mothers flexibly adapt and coordinate the different components of maternal behavior with other motivated behaviors, also critical for the survival of the species.

Maternal condition reduces fear behaviors but not the endocrine response to an emotional threat in virgin female rats.

Lactating dams and maternal virgin females are less fearful in behavioral tests compared with non-maternal animals, suggesting that maternal condition per se reduces the negative value of threatening stimuli. In addition, lactating females exhibit a diminished hypothalamic-pituitary-adrenal response to potential environmental threats. Can the maternal condition, independently of the endocrine profile of lactation, promote a reduction in the behavioral as well as in the endocrine response to an emotional stressor? To answer this question, anxiety-related and fear behaviors as well as the levels of corticosterone were evaluated in response to a bright-lit open field-loud noise model in maternal and non-maternal non-ovariectomized virgin females and lactating dams in the presence of the pups. Maternal animals, both lactating and virgin, presented an increased exploration of the bright-lit open field and a significant reduction of fear behaviors, indicated by the decreased flight and immobility responses to the subsequent activation of a loud noise, in comparison to non-maternal virgins. Interestingly, maternal virgin females, as non-maternal rats, showed high corticosterone plasma levels, in contrast to the lower endocrine response exhibited by lactating dams when confronted to this threat. Present results suggest that maternal condition allows females to take risks when caring for their young, a behavioral strategy that is independent of the reduced hypothalamic-pituitary-adrenal axis response characteristic of lactation. This evidence points towards a clear dissociation in the mechanisms regulating behavioral and endocrine responses to emotional stressors during motherhood.

Ovarian steroids counteract serotonergic drugs actions in an animal model of obsessive-compulsive disorder

Recently, we reported the existence of differences according to the reproductive stage of female rats in a pharmacologically induced animal model of obsessive-compulsive disorder. Therefore, the aim of the present study was to examine the role of endogenous and exogenous ovarian steroids in the induction of perseverative responses in a T-maze by the 5-HT1A agonist 8-OH-DPAT (1.0 and 2.0 mg/kg, SC) and in the preventive action of the selective serotonin reuptake inhibitor, fluoxetine (10.0 mg/kg, three times, SC). The results showed that the perseverant action of 8-OH-DPAT as well as the prevention of such perseverance by fluoxetine were reduced during the estrous-metestrous phases of the female reproductive cycle, and by the exogenous ovarian steroids administration to ovariectomized animals. Data are discussed from the standpoint of the action of ovarian steroids on the serotonergic system and on the putative influence of these hormones on the physiopathology and treatment of this disorder in women.

Melanin-concentrating hormone in the medial preoptic area reduces active components of maternal behavior in rats.

Melanin-concentrating hormone (MCH) is an inhibitory neuropeptide mainly synthesized in neurons of the lateral hypothalamus and incerto-hypothalamic area of mammals that has been implicated in behavioral functions related to motivation. During lactation, this neuropeptide is also expressed in the medial preoptic area (mPOA), a key region of the maternal behavior circuitry. Notably, whereas MCH expression in the mPOA progressively increases during lactation, maternal behavior naturally declines, suggesting that elevated MCHergic activity in the mPOA inhibit maternal behavior in the late postpartum period. To explore this idea, we assessed the maternal behavior of early postpartum females following bilateral microinfusions of either MCH (50 and 100 ng/0.2 μl/side) or the same volume of vehicle into the mPOA. As expected, females receiving 100 ng MCH into the mPOA exhibited significant deficits in the active components of maternal behavior, including retrieving and nest building. In contrast, nursing, as well as other behaviors, including locomotor activity, exploration, and anxiety-like behavior, were not affected by intra-mPOA MCH infusion. The present results, together with previous findings showing elevated expression of this neuropeptide toward the end of the postpartum period, suggest that modulation of mPOA function by MCH may contribute to the weaning of maternal responsiveness characteristic of the late postpartum period.

The Reproductive Stage and Experience of Sexually Receptive Mothers Alter Their Preference for Pups or Males

Female rats show postpartum estrus, a unique stage in their reproductive cycle in which they are able to display maternal and sexual responses at the same time. To assess the relative value of pups or males for sexually receptive mothers with different hormonal profiles and reproductive experiences, we employed a 3-point star maze with 3 choice compartments containing: pups, a sexually active male, or no stimulus (neutral). Cycling maternal and nonmaternal females in late proestrus, independently of their previous reproductive experience, strongly preferred the male to the pups, although most postpartum estrous dams did not exhibit preference for the male. The majority of the postpartum primiparous females did not prefer the litters chamber either, but a previous reproductive experience strongly determined their preference for the pups. These results suggest that the hormonal changes of the proestrus, in contrast to those of the postpartum estrus, promote a strong preference for the male that is not diminished by the maternal condition. Conversely, the endocrine changes of the postpartum facilitate the effect of previous reproductive experience in strengthening the incentive value of the pups.

Coexpression of Sexual Behavior and Maternal Aggression: The Ambivalence of Sexually Active Mother Rats Toward Male Intruders

The sexually active female rat solicits the male to approach for copulation, while the maternal dam displays aggression to expel him from the nest, suggesting that both behaviors are mutually exclusive. However, the rat has a postpartum estrus during which she is sexual and maternally motivated. Can she perceive the male as attractive and aversive, soliciting and attacking him at the same time? This study shows that postpartum estrous females exhibit a merge of sexual and maternal aggressive responses toward male intruders in the home cage. The concurrent expression of these behaviors did not affect their intensities, although the stimulation of maternal behavior increased maternal aggression without modifying sexual solicitation. These results indicate that the postpartum estrous rat can optimally express two opposite and independently regulated motivations, and that the male can be perceived as an ambivalent stimulus.