Michael Numan

Medial preoptic area interactions with dopamine neural systems in the control of the onset and maintenance of maternal behavior in rats.

The medial preoptic area (MPOA) and dopamine (DA) neural systems interact to regulate maternal behavior in rats. Two DA systems are involved: the mesolimbic DA system and the incerto-hypothalamic DA system. The hormonally primed MPOA regulates the appetitive aspects of maternal behavior by activating mesolimbic DA input to the shell region of the nucleus accumbens (NAs). DA action on MPOA via the incerto-hypothalamic system may interact with steroid and peptide hormone effects so that MPOA output to the mesolimbic DA system is facilitated. Neural oxytocin facilitates the onset of maternal behavior by actions at critical nodes in this circuitry. DA-D1 receptor agonist action on either the MPOA or NAs can substitute for the effects of estradiol in stimulating the onset of maternal behavior, suggesting an overlap in underlying cellular mechanisms between estradiol and DA. Maternal memory involves the neural plasticity effects of mesolimbic DA activity. Finally, early life stressors may affect the development of MPOA-DA interactions and maternal behavior.

Functional Magnetic Resonance Imaging Shows Oxytocin Activates Brain Regions Associated with Mother–Pup Bonding during Suckling

Oxytocin is released in the maternal brain during breastfeeding and may help strengthen the mother–infant relationship. Here, we used functional magnetic resonance imaging to determine whether oxytocin modulates brain activity in postpartum day 4–8 dams receiving suckling stimulation. During imaging sessions, dams were exposed to pup suckling before and after administration of an oxytocin receptor antagonist. Another group of dams received oxytocin alone. Changes in brain activation in response to suckling closely matched that elicited by oxytocin administration. The overlapping brain areas included the olfactory system, nucleus accumbens, insular cortex, prefrontal cortex, ventral tegmental area, cortical amygdala, and several cortical and hypothalamic nuclei. Blockade of oxytocin receptors largely attenuated activation in these regions. The data suggest that oxytocin may strengthen mother–infant bond formation partly by acting through brain areas involved in regulating olfactory discrimination, emotions, and reward.

Neuroanatomical Circuitry for Mammalian Maternal Behavior

This paper presents an overview of the neural circuitry underlying maternal behavior in mammals. Because most of this work has been done on the rat, our review concentrates on that species. The hormonal events of late pregnancy, in particular, rising estrogen and prolactin levels and declining progesterone levels, are necessary for stimulating the onset of maternal behavior at parturition in primiparous females of many mammalian species.’ An important process to understand is the neural mechanisms influenced by ‘‘maternal hormones.” Several recent reviews argue that maternal behavior is facilitated when the tendency to approach infant stimuli and engage in maternal behavior is greater than the tendency to avoid or withdraw from such stimuli.’“ This kind of analysis suggests that the hormonal events of late pregnancy act on brain mechanisms to either decrease fear/aversion of infant stimuli or increase attractiodapproach towards infant stimuli, or both. These possibilities are illustrated in FIGURE 1. Several pieces of evidence support this scheme: (1) Nulliparous females of many mammalian species avoid or attack neonates.‘ Indeed, nulliparous female rats move out of the preferred part of their home cage if pups are placed there? (2) Although nonpregnant rats and sheep either show no preference for or actively avoid olfactory stimuli associated with neonates, animals that have been exposed to the hormonal events of late pregnancy show a strong attraction to such (3) Although the nulliparous female rat will not show immediate maternal responsiveness towards its young, if she is cohabited with them, she will come to show maternal behavior after about 5-7 days.’ This latency to respond can be shortened by a hormone regimen that mimics the endocrine changes of late pregnancy.’ Importantly, this latency can also be reduced in nonhormone-primed nulliparous females by making them anosmic.* Such females show maternal behavior after about only 24 hours of pup exposure. These findings have been interpreted to mean that nulliparous females find olfactory stimuli from young aversive and that maternal behavior will occur only after the aversive nature of such stimuli has been reduced by either habituation, hormonal effects, or experimentally induced a n ~ s m i a . ~ , ~ The effects of anosmia on maternal behavior in nulliparous rats support the model shown in FIGURE 1A: approach and attraction to nonolfactory stimuli may be relatively high in the absence of hormone treatment, and the hormonal events of late pregnancy downregulate the aversionproducing influence of pup odors.’ However, the fact that anosmic virgins do not

Maternal behavior in rats: evidence for the involvement of preoptic projections to the ventral tegmental area.

This study provides evidence that a neural system extending from the preoptic region to the ventral tegmental area (VTA) of the midbrain is important for the normal expression of maternal behavior in lactating rats. In the first experiment, bilateral electrolytic lesions of the VTA severely disrupted the maternal behavior of postpartum rats. In the second experiment, lactating rats that received a unilateral knife cut severing the lateral connections of the medial preoptic area (MPOA) paired with a contralateral lesion of the VTA showed more severe maternal behavior deficits than females that received one of the following treatments: (a) a unilateral knife cut severing the lateral connections of the MPOA paired with an ipsilateral VTA lesion; (b) a unilateral knife cut severing the lateral connections of the MPOA paired with a contralateral lesion of the medial hypothalamus posterior to the MPOA; (c) a unilateral knife cut severing the lateral connections of the lateral preoptic area paired with a contralateral VTA lesion. The oral components of maternal behavior (retrieving and nest building) were particularly affected as a result of bilateral damage to the system extending from the preoptic area to the VTA.

Axon-sparing lesions of the preoptic region and substantia innominata disrupt maternal behavior in rats

In this study we investigated the effects of axon-sparing lesions of the preoptic region on the maternal behavior of postpartum rats. The lesions were produced with the excitotoxic amino acid N-methyl-D,L-aspartic acid (NMA). The first experiment determined that bilateral injections of NMA into the medial preoptic area (MPOA) of fully maternal lactating rats disrupted maternal behavior. In a second experiment, bilateral injections of NMA into the lateral preoptic area and adjoining substantia innominata (LP/SI region) also disrupted maternal behavior. A third experiment, employing horseradish peroxidase histochemistry, provided anatomical evidence that NMA destroys neuronal cell bodies while sparing fibers of passage. These findings were discussed with respect to the view that an MPOA-to-LP/SI-to-ventral tegmental area circuit underlies maternal behavior in the rat.

A lesion and neuroanatomical tract-tracing analysis of the role of the bed nucleus of the stria terminalis in retrieval behavior and other aspects of maternal responsiveness in rats

The ventral part of the bed nucleus of the stria terminalis forms a junctional region between the medial and lateral preoptic areas. Previous work has shown that the neurons in this region express Fos-like immunoreactivity during maternal behavior, suggesting their involvement in maternal behavior control. Supporting this hypothesis, the first experiment shows that excitotoxic amino acid lesions of the bed nucleus of the stria terminalis disrupt retrieval behavior and other aspects of maternal responsiveness in postpartum rats. The second study traces the efferent projections of the ventral bed nucleus with the anterograde tracer Phaseolis vulgaris leucoagglutinin. The following regions receive strong projections: lateral septum, substantia innominata, paraventricular hypothalamic nucleus, ventral premammillary nucleus, supramammillary nucleus, paraventricular thalamus, ventral tegmental area, periaqueductal gray, retrorubral field, and the region surrounding the locus coeruleus.

Expression of Fos-like immunoreactivity in the preoptic area of maternally behaving virgin and postpartum rats.

This study uses Fos immunocytochemistry to show that the medial preoptic area and ventral bed nucleus of the stria terminalis are activated in maternally behaving female rats. In Experiment 1, virgin female rats that showed maternal behavior toward pups had more cells in these regions that expressed Fos-like immunoreactivity than did virgin females that were not maternally responsive. In Experiment 2, postpartum rats that were exposed to pups and showed maternal behavior had more Fos-labeled cells in these regions than did postpartum rats exposed to candy. Evidence also indicated that functional modifications in the medial amygdala were related to the changes in Fos expression observed in the preoptic area and ventral bed nucleus of the stria terminalis.

The effects of D1 or D2 dopamine receptor antagonism in the medial preoptic area, ventral pallidum, or nucleus accumbens on the maternal retrieval response and other aspects of maternal behavior in rats

The medial preoptic area (MPOA), ventral pallidum (VP), and nucleus accumbens (NA) receive dopaminergic afferents and are involved in maternal behavior. Experiments investigated whether dopamine (DA) receptor antagonism in NA disrupts maternal behavior, determined the type of DA receptor involved, and investigated the involvement of drug spread to VP or MPOA. Injection of SCH 23390 (D1 DA receptor antagonist) into NA of postpartum rats disrupted retrieving at dosage levels that were ineffective when injected into MPOA or VP. Motor impairment was not the cause of the deficit. Injection of eticlopride (D2 DA receptor antagonist) into NA or VP was without effect. Results emphasize the importance of DA action on D1 receptors in NA for retrieval behavior.

The connections of the medial preoptic region and maternal behavior in the rat

Abstract Female rats which are hysterectomized and ovariectomized on Day 16 of pregnancy and injected with estrogen show a short latency to onset of maternal behavior when presented with test pups 48 hrs later. In the present experiment, female rats were treated similarly except that on Day 16 of pregnancy they received knife cuts which severed either the lateral, anterior, dorsal, or posterior connections of the medial preoptic area (MPOA), or sham knife cuts. Severing the lateral connections of the MPOA severely disrupted materal behavior, while severing the dorsal or posterior connections of the MPOA produced either minor deficits or no deficits. Severing the anterior connections of the MPOA did produce large deficits in maternal behavior, but this was associated with hypoactivity and loss of body weight. Therefore, the maternal behavior deficits observed in the anterior cut group may have been a secondary effect of the knife cut. The results emphasize the importance of the lateral connections of the MPOA for maternal behavior.

Importance of pup-related sensory inputs and maternal performance for the expression of Fos-like immunoreactivity in the preoptic area and ventral bed nucleus of the stria terminalis of postpartum rats.

This study used Fos immunocytochemistry to locate neurons within the medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBNST) that are tightly associated with the performance of maternal behavior in postpartum rats. In the first experiment, a high degree of Fos activation was observed in these regions if females were allowed to interact fully with pups, but not if they could receive only olfactory, visual, and auditory inputs from pups. The second experiment found that olfactory bulbectomy combined with thelectomy did not eliminate Fos expression in the MPOA and VBNST of females displaying maternal behavior. These Fos-expressing neurons may represent efferent neurons essential for the performance of maternal behavior.