Jay Rosenblatt's approach-avoidance model of maternal behavior proposes that maternal behavior occurs when the tendency to approach infant stimuli is greater than the tendency to avoid such stimuli. Our research program has uncovered neural circuits which conform to such a model. We present evidence that the medial preoptic area (MPOA: located in the rostral hypothalamus) may regulate maternal responsiveness by depressing antagonistic neural systems which promote withdrawal responses while also activating appetitive neural systems which increase the attractiveness of infant-related stimuli. These MPOA circuits are activated by the hormonal events of late pregnancy. Preoptic efferents may suppress a central aversion system which includes an amygdala to anterior hypothalamic circuit. Preoptic efferents are also shown to interact with components of the mesolimbic dopamine (DA) system to regulate proactive voluntary maternal responses. We make a distinction between specific (MPOA neurons) and nonspecific motivational systems (mesolimbic DA system) in the regulation of maternal responsiveness.

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Mother-infant bonding is a characteristic of virtually all mammals. The maternal neural system may have provided the scaffold upon which other types of social bonds in mammals have been built. For example, most mammals exhibit a polygamous mating system, but monogamy and pair bonding between mating partners occurs in ∼5% of mammalian species. In mammals, it is plausible that the neural mechanisms that promote mother-infant bonding have been modified by natural selection to establish the capacity to develop a selective bond with a mate during the evolution of monogamous mating strategies. Here we compare the details of the neural mechanisms that promote mother-infant bonding in rats and other mammals with those that underpin pair bond formation in the monogamous prairie vole. Although details remain to be resolved, remarkable similarities and a few differences between the mechanisms underlying these two types of bond formation are revealed. For example, amygdala and nucleus accumbens-ventral pallidum (NA-VP) circuits are involved in both types of bond formation, and dopamine and oxytocin action within NA appears to promote the synaptic plasticity that allows either infant or mating partner stimuli to persistently activate NA-VP attraction circuits, leading to an enduring social attraction and bonding. Further, although the medial preoptic area is essential for maternal behavior, its role in pair bonding remains to be determined. Our review concludes by examining the broader implications of this comparative analysis, and evidence is provided that the maternal care system may have also provided the basic neural foundation for other types of strong social relationships, beyond pair bonding, in mammals, including humans.

The present series of experiments examined whether the medial preoptic area (MPOA) is involved in the onset of maternal behavior in the rat. Previously, the MPOA had been shown to be important in the maintenance of maternal behavior in the lactating rat. The first experiment investigated whether estradiol benzoate (EB) acts on the MPOA to facilitate the onset of maternal behavior in the 16-day pregnant, hysterectomized, and ovariectomized female rat. Such rats when given EB implants in the MPOA had significantly shorter latencies for the onset of maternal behavior than had females implanted with cholesterol in the MPOA or with EB in the ventromedial hypothalamus, in mammillary bodies, or under the skin. A second experiment showed that estrogen-induced prolactin release was not involved in this facilitation. A third experiment indicated that MPOA lesions disrupt the onset of maternal behavior that is induced by pup stimulation in virgin females. It was concluded that the MPOA is involved not only in the maintenance of maternal behavior but in the hormonally mediated onset of maternal behavior and the onset of maternal behavior induced in virgin females by pup stimulation.

In rodents, previous findings indicate critical involvement of the medial preoptic area (MPOA) in the neural control of maternal behavior. However, the specification of the particular MPOA subregions involved in maternal behavior and the identification of the neurochemical phenotype(s) of the essential neurons demands additional study. Therefore, we investigated the chemical neuroanatomy of the essential MPOA subregion for maternal behavior in C57BL/6J female mice. Using the oxytocinergic neurons in the dorsal MPOA as a primary regional marker, we first assessed the distribution of c-Fos-expressing neurons in the MPOA during maternal behavior using immunohistochemistry. Results showed that non-oxytocinergic neurons in the dorsal and ventral MPOA prominently expressed c-Fos during maternal behavior. Then using excitotoxic lesion studies, we determined the specific MPOA area that is necessary for maternal behavior. Bilateral lesions of the central MPOA, where c-Fos was expressed only moderately, effectively disrupted maternal behavior, although lesions to the dorsal and ventral MPOA regions were ineffective. These centrally lesioned females were highly infanticidal irrespective of their previous maternal experience. Neurochemical investigations showed that more than 75% of the c-Fos-expressing neurons in central MPOA were GABAergic. Many of them also expressed galanin, neurotensin, and/or tachykinin2 mRNAs. Finally, the central MPOA was populated by numerous glutamatergic neurons, although only a small percentage of these neurons colocalized with c-Fos. To conclude, the central MPOA is the indispensable subregion for mouse maternal behavior, and GABAergic and/or peptidergic neurons in this area were transcriptionally activated during maternal behavior.

A series of experiments were conducted to determine whether and under what conditions central prolactin (PRL) administration would stimulate the onset of maternal behavior in female rats and to identify possible neural sites of PRL action. In each experiment ovariectomized, nulliparous rats whose endogenous PRL levels were suppressed with bromocriptine were tested for maternal behavior toward foster young. In experiments 1, 2, and 4, females were also exposed to pregnancy-like levels of progesterone (days 1-11) followed by estradiol (days 11-17). In experiment 1 infusions (days 11-13) of four doses of ovine PRL (400 ng, 2 ,ug, 10 ,ug, or 50 jug, but not 80 ng) into the lateral ventricle resulted in a rapid onset of maternal behavior (behavioral testing, days 12-17). The stimulatory action of these doses of PRL appears to be central, since subcutaneous injections of 50 jug of ovine PRL failed to affect maternal responsiveness (experiment 2). Experiment 3 indicated that the stimulatory effect of intracerebroventricularly administered PRL is steroid dependent. Infusions of either 10 ,ug of ovine PRL or 10 1ug of rat PRL failed to induce maternal behavior in nonsteroid-treated animals. In the final experiment (no. 4) bilateral infusions of 40 ng of ovine PRL into the medial preoptic area of steroid-treated rats resulted in a pronounced stimulation of maternal behavior. These findings demonstrate a central site of PRL action in the stimulation of maternal responsiveness and point to the medial preoptic area as a key neural site for PRL regulation of maternal behavior.The hormonal changes accompanying pregnancy and parturition play a critical role in preparing the female to respond maternally toward her newborn young (1-4). One hormone that recently was shown to have a key role in inducing maternal behavior is the pituitary hormone prolactin (PRL) (5, 6). PRL and other members of the PRL family-i.e., growth hormone and placental lactogens-are secreted in large amounts during pregnancy (7-9), making these molecules potential physiological regulators of maternal behavior. Eliminating or suppressing PRL secretion in steroid-treated, ovariectomized, nulliparous rats by either hypophysectomy or administration of bromocriptine, a dopamine agonist, blocks the rapid onset of maternal behavior (5, 6). These effects are prevented when PRL is given to hypophysectomized or bromocriptine-treated female rats.Although PRL stimulates the onset of maternal behavior, little is known about PRL's site of action. The purpose of the present report was to investigate the possibility that PRL acts at the level of the central nervous system to stimulate maternal behavior. A central site of PRL action is feasible in light of a series of findings that indicate that circulating PRL can gain access to the brain through active transport across the blood-cerebrospinal fluid (CSF) barrier (10), that PRL, presumably of pituitary origin, is found in increased amounts within the CSF at times when circulating levels of PRL are elevated (11-13), ...

A theoretical neural model is developed, along with supportive evidence, to explain how the medial preoptic area (MPOA) of the hypothalamus can regulate maternal responsiveness toward infant-related stimuli. It is proposed that efferents from a hormone-primed MPOA (a) depress a central aversion system (composed of neural circuits between the amygdala, medial hypothalamus, and midbrain) so that novel infant stimuli do not activate defensive or avoidance behavior and (b) excite the mesolimbic dopamine system so that active, voluntary maternal responses are promoted. The effects of oxytocin and maternal experience are included in the model, and the specificity of MPOA effects are discussed. The model may be relevant to the mechanisms through which other hypothalamic nuclei regulate other basic motivational states. In addition, aspects of the model may define a core neural circuitry for maternal behavior in mammals.

In postpartum lactating female rats, medial preoptic area lesions severely disrupted maternal behavior. Lesions of the stria terminalis and medial cortico-hypothalamic tract knife cuts were without effect. Parasagittal knife cuts that severed the mediolateral connections of the preoptic-anterior hypothalamic continuum also severely disrupted maternal behavior. The lesions and knife cuts which disrupted maternal behavior had no effect on female sexual behavior. It was concluded that the medial preoptic area and its lateral connections are essential for the normal display of maternal behavior in postpartum lactating female rats. Furthermore, evidence has been advanced which indicates that independent neural mechanisms for the control of maternal behavior and sexual behavior exist within the hypothalamus of female rats.