Estrogen receptor-alpha knockouts and maternal memory in nulliparous rats.

The current study investigated the role of estrogen receptor alpha (Esr1) in maternal memory in rats, comparing the induction and retention responses of Esr1 knockout (KO) and wild type (WT) nulliparous rats towards foster pups. Thirty days after completion of induction testing, subjects were tested for the retention of maternal care in their home cage and then for maternal behaviors in a novel cage. Both WT and Esr1 KO females displayed similar latencies to respond to foster young during the initial induction testing. Likewise, reinduction latencies to display full maternal responsiveness were similar in the Esr1 KO and WT groups during maternal memory testing in the home cage. However, in the novel cage testing WT subjects displayed modest modifications in maternal care. WT females had shorter latencies to first retrieve and mouth a test pup. These findings suggest that while Esr1 does not appear to affect the establishment of maternal care or the display of maternal memory, it may modulate aspects of pup-directed behaviors associated with the reinduction of maternal care in female rats.

Reproductive experience alters neural and behavioural responses to acute oestrogen receptor α activation.

Reproductive experience (i.e. parturition and lactation) leads to persistent alterations in anxiety-like behaviour that are influenced by the oestrous cycle. We recently found that repeated administration of the selective oestrogen receptors (ER)α agonist propyl-pyrazole triol (PPT) results in anxiolytic-like behaviours on the elevated plus maze (EPM) in primiparous (but not nulliparous) female rats. The present study examined the effects of the acute administration of PPT on EPM behaviour in primiparous and aged-matched, nulliparous female rats. In addition, corticosterone secretion, corticotrophin-releasing hormone (CRH) gene expression and expression of the immediate early gene product Fos in the paraventricular nucleus (PVN) and amygdala were measured either after EPM testing or in home cage controls. Acute PPT administration significantly modified EPM behaviour as a function of reproductive experience, with nulliparous females tending toward increased anxiety-like behaviours and primiparous females tending toward decreased anxiety-like behaviours. In home cage controls, PPT increased corticosterone secretion in all females; however, both vehicle- and PPT-treated, primiparous females had reduced corticosterone levels compared to their nulliparous counterparts. Significant effects of PPT on CRH mRNA within the PVN were observed after the administration of PPT but only in primiparous females tested on the EPM. PPT also increased Fos expression within the PVN of EPM-exposed females; however, both vehicle- and PPT-treated primiparous females had reduced Fos expression compared to nulliparous females. In the amygdala, PPT increased Fos immunoreactivity in the central but not the medial or basolateral amygdala, although these effects were only observed in home cage females. Additionally, both vehicle- and PPT-treated home cage, primiparous females had increased Fos in the central nucleus of the amygdala compared to nulliparous controls. Overall, these data demonstrate that reproductive experience alters the behavioural response to acute ERα activation. Moreover, the findings suggest that central regulation of the hypothalamic-adrenal-pituitary axis is modified as a consequence of reproductive experience.

Differential expression of oestrogen receptor alpha following reproductive experience in young and middle-aged female rats.

Reproductive experience (i.e. pregnancy and lactation) alters a number of physiological and behavioural endpoints, many of which are related to reproductive function and are regulated by oestrogen. For example, reproductive experience significantly attenuates the oestradiol-induced prolactin surge on the afternoon of pro-oestrous and circulating oestradiol levels are reduced at this time. Although parity-related effects on oestrogen receptor (ER) alpha have been observed within the anterior pituitary, there are currently no data regarding possible parity-induced alterations in ERalpha in the brain. Thus, the present study aimed to examine the effect of parity on the expression of ERalpha in reproductively relevant brain regions. Moreover, because previous findings have demonstrated that the long-term effects of reproductive experience are often oestrous cycle-dependent, ERalpha was examined at two stages of the oestrous cycle (i.e. dioestrous and pro-oestrous). Finally, because the expression of ERalpha is significantly influenced by age, both young and middle-aged females were included in the present study. ERalpha status was determined using immunohistochemistry in select brain regions involved in the regulation of reproductive behaviour in age-matched, cycling primiparous (i.e. one pregnancy and lactation) and nulliparous females as well as in age-matched, noncycling (i.e. persistent oestrous) 12 month-old primiparous and nulliparous females. Significant shifts in ERalpha cell numbers were observed in the medial preoptic area and medial amygdala as a consequence of reproductive experience in an oestrous-dependent manner. These findings indicate that significant changes in ERalpha activity occur in the brain as a function of reproductive experience.

Reproductive experience and expression of dopamine D(2) receptor mRNA: a possible mechanism for reduced prolactin secretion in primiparous rats.

Reproductive experience (i.e. pregnancy and lactation) leads to reduced levels of circulating prolactin in both women and rats. Stimulation of prolactin secretion by dopamine antagonists is also blunted following reproductive experience in both species. Whereas a parity-induced reduction in haloperidol-stimulated prolactin secretion is evident in ovariectomised rats, it is unknown whether a similar attenuation of prolactin secretion is present in reproductively experienced, cycling pro-oestrous rats. The present study examined this possibility. Moreover, to determine possible mechanisms involved in parity-mediated changes in prolactin secretion, both dopamine utilisation within the arcuate nucleus/median eminence and expression of dopamine D(2) receptor mRNA (short and long forms) in the anterior pituitary were measured across the afternoon of pro-oestrous in reproductively experience and inexperienced females. Prolactin secretion was lower on the afternoon of pro-oestrous in primiparous females compared to age-matched, nulliparous controls. In addition, haloperidol-stimulated prolactin secretion was reduced in ovariectomised, reproductively experienced females. Although no differences in dopamine utilisation were observed as a function of reproductive experience, parity did affect the expression of both forms of D(2) receptor mRNA in the anterior pituitary. Compared with nulliparous controls, primiparous females had increased D(2 long) mRNA expression at 12.00 h on pro-oestrous as well as increased D(2 short) mRNA expression at 14.00 h. Because the ratio of D(2 long)/D(2 short) can significantly effect lactotroph proliferation and prolactin secretion, a shift in relative expression of the two D(2) receptor isoforms within the anterior pituitary of parous females may help account for the reduction in prolactin secretion that occurs following reproductive experience.

Intracerebroventricular administration of the prolactin (PRL) receptor antagonist, S179D PRL, disrupts parturition in rats.

The prolactin (PRL) receptor antagonist S179D PRL delays the onset of maternal behavior in steroid-primed nulliparous female rats. The present study investigated the role of the neural PRL system in the process of parturition. A preliminary study indicated that S179D PRL treatments administered by ALZET minipump to the lateral ventricle severely disrupted parturition. To examine the likely causes of this disruption, a group of timed-pregnant catheterized rats was continuously infused with S-179D PRL (0.001 and 0.1 ng/h) or vehicle control to the lateral ventricles for 3 days (gestation days 21-23), and serial blood samples were taken throughout this period. Effects of the treatments on parturition were recorded, and blood samples were assayed for PRL, progesterone, and oxytocin. Significantly fewer S179D PRL-treated rats successfully delivered by 1500 h on day 23 of gestation when compared with controls. The higher dose of S179D PRL also significantly suppressed the prepartum rise in PRL throughout the prepartum period, while the lower dose only affected plasma PRL during the first 24 h of treatment. No significant effects of the antagonist on plasma progesterone or oxytocin were detected. We conclude that disruption of parturition by S179D PRL is not caused by significant alterations in the plasma concentrations of progesterone or oxytocin. S179D PRL may indirectly act on parturition through the modulation of prepartum PRL. These findings suggest a previously unrecognized role for PRL in the regulation of parturition.

The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin

This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant

Lactogenic hormone regulation of maternal behavior.

Biological factors can profoundly affect a mother's response to her young. For example, it is well known that the hormones of pregnancy act on the maternal brain to stimulate the spontaneous onset of maternal behavior at parturition. Studies in the rat have provided an excellent model to investigate maternal behavior in mammals, since maternal behavior in rats is easily observable and readily quantifiable and it is well-documented that the endocrine state of gestation helps to bring about the onset of maternal behavior around the time of birth. The same response in virgin animals requires a number of days of constant exposure to pups before maternal-like behaviors emerge. To date, research has established that the steroid hormones, estradiol and progesterone, and the lactogenic hormones, prolactin and the placental lactogens, act in concert to stimulate maternal behavior in the pregnant female. Treatment of adult, virgin rats with these hormones can stimulate a rapid onset of maternal care. In the present chapter experiments are described that demonstrate key roles for prolactin and placental lactogens in the onset of maternal behavior. Central sites of action of prolactin and placental lactogens, including the medial preoptic area, appear to be involved in stimulating the onset of maternal care. Other studies are discussed which support the involvement of the prolactin receptor in the endocrine regulation of maternal behavior using prolactin receptor antagonist and 'knock-out' models in rats and mice, respectively. Overall, these studies indicate that during pregnancy the endocrine system primes the mother's brain so that the new mother displays appropriate and successful behaviors toward her newborn at parturition.

The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin.

This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant.

Increased sensitivity of dopamine systems following reproductive experience in rats.

Several studies have suggested that alterations in forebrain dopamine activity during the postpartum period may result in the onset of postpartum psychosis in women [J. Psychosom. Obstet. Gynecol. 19 (1998) 104; Prog. Neuro-Psychopharmacol. Biol. Psychiatry 17 (1993) 571; J. Clin. Psychiatry 51 (1990) 365.]. The present study investigated whether increased dopamine activity in these forebrain regions is a normal consequence of reproductive experience in rodents. Both intact and ovariectomized parous and nulliparous females were tested for their responses to the dopamine agonist apomorphine using two behavioral measures, prepulse inhibition (PPI) and oral stereotypy. In addition, dopamine and DOPAC levels were measured in tissue from the striatum and nucleus accumbens together with circulating plasma prolactin levels. The results of the behavioral studies demonstrate an increased response to apomorphine in parous females. Parous subjects also had increased levels of dopamine and DOPAC in striatal tissue and lower levels of circulating prolactin. Ovariectomy in nulliparous females resulted in a potentiated response to apomorphine with regard to the disruption of PPI, as well as a significant decrease in the plasma prolactin levels, as compared with intact nulliparous females. These data suggest that increased dopamine activity in forebrain regions occurs as a consequence of parity, which persists for a minimum of several weeks postpartum. These findings support the hypothesis that increased dopamine sensitivity in forebrain dopamine regions may be one potential mechanism underlying the development of postpartum psychosis in women.

Opioid receptor antagonism during early lactation results in the increased duration of nursing bouts.

High levels of mu opioid receptor activation during the postpartum period result in the disruption of ongoing maternal behavior. The role of physiological levels of endogenous opioids on the mediation of maternal behavior in postpartum females, however, has not been closely examined. The purpose of the present experiments was to examine the function of endogenous opioids during early and mid-lactation by treating postpartum females with the opioid antagonist naloxone and monitoring their behavioral interactions with pups. Although this treatment did not lead to any qualitative differences in the maternal behaviors measured (pup retrieval and grooming, nest building, grouping of pups, or crouching over pups), there was a quantitative difference in the amount of time the females spent with pups on the nest and actively nursing pups. Naloxone, given either systemically or centrally (intracerebroventricularly), resulted in prolonged nursing and nesting bouts. This effect, however, was only observed during the early lactation time point (postpartum days 5-7). Females tested later in lactation (postpartum days 10-12 or 12-14) did not display the increased nursing or nesting bouts in response to the antagonist. These data indicate that central opioids play a role in the duration of nursing bouts during early lactation.

Endogenous opioid facilitation of maternal memory in rats.

In rats, contact with pups at parturition establishes a form of maternal memory that enables female rats to respond rapidly to pups in the future. Treatment of pregnant female rats with the long-lasting micro opioid receptor antagonist, beta-funaltrexamine (beta-FNA), prior to parturition interfered with the establishment of maternal memory. Similar treatment 3 hr postpartum resulted in disrupted retention of maternal memory that appeared nonspecific, with both drug- and vehicle-treated rats displaying a deficit. However, infusion of the opioid antagonist 24 hr postpartum had no effect on the retention of maternal memory tested 7 days later. These findings indicate that the establishment of maternal memory is mediated by endogenous opioid activity around the time of parturition.

Expression of mu-opioid receptor mRNA in the medial preoptic area of juvenile rats.

Previous studies indicate that the latency to initiate parental behavior in both male and female rats increases with age; weanling (21 days old) rats display parental behavior 0-2 days after exposure to newborn pups, while older juveniles (30 days old) require 5-6 days of pup exposure before they express the behavior. Furthermore, activation of mu-opioid receptors inhibits parental behavior in juvenile and adult rats. We hypothesized that the age-related increase in behavioral latency could be modulated by the induction of mu-receptor expression in the medial preoptic area (MPOA), a region in which mu-receptors regulate parental behavior. In situ hybridization histochemistry was used to measure mu-receptor mRNA expression in the MPOA of male and female Sprague-Dawley rats that were 21, 24, 27, 30, or 33 days old. Using autoradiographic film analysis, we observed that neurons within part of the MPOA expressed very dense mu-receptor mRNA. Comparison of mRNA distribution with histological boundaries indicated that neurons within the medial preoptic nucleus (MPN), excluding the central part, exhibited the highest density of mu-receptor mRNA within the MPOA. High densities of mu-receptor mRNA extended dorsolaterally and caudally from the MPN toward the bed nucleus of the stria terminalis. MPN mu-receptor mRNA expression was not altered with age and no sex difference was observed. The dense presence of mu-receptor mRNA in the MPN suggests that ample substrate exists on which mu-receptor ligands could modulate the latency to begin parental behavior in juvenile rats, but such behavioral expression apparently is not mediated by a change in mu-receptor mRNA production.

The development of POMC gene expression in the medial basal hypothalamus of prepubertal rats.

Alterations in brain opioid gene expression may underlie the dramatic change in the latency to display parental behavior in juvenile rats. Male and female juvenile rats (18-25 days of age) exhibit parental behavior either immediately or within 1-2 days after coming in contact with foster pups. By 30 days of age, however, their response latencies increase to adult levels of 5-10 days. Given the established involvement of the endogenous opioid system in adult maternal and juvenile parental behaviors, the objective of the present report was to determine possible changes in proopiomelanocortin (POMC) gene expression in the medial basal hypothalamus (MBH) during this early developmental window. We compared POMC gene expression in the MBH of male and female juvenile rats from 21 to 33 days of age by in situ hybridization histochemistry. A significant increase in the number of POMC cells in males and females was detected at 30 days of age in the central portion of the arcuate nucleus. This increase in POMC mRNA may contribute to the shift in parental behavior that occurs in male and female juvenile rats.

Hypothalamic involvement in the regulation of maternal behaviour in the rat: inhibitory roles for the ventromedial hypothalamus and the dorsal/anterior hypothalamic areas.

The present report examines the possible involvement of the ventromedial hypothalamus (VMH), the dorsal hypothalamus (DH), and the anterior hypothalamic area (AHA) in the regulation of maternal behaviour in the female rat. In a series of experiments it was found that either infusions of saline or lowering cannulas into the VMH stimulated a rapid onset of maternal behaviour in progesterone plus oestrogen-primed, nulliparous rats. The stimulatory effect of cannula lowering into the VMH on maternal behaviour was shown to be steroid-dependent. Next, the involvement of cell bodies located in the DH/AHA in maternal behaviour was examined after bilateral lesions of these regions with the neurotoxin, N-methyl-D-aspartic acid (NMA). NMA lesions of the DH/AHA stimulated a rapid onset of maternal behaviour in oestrogen-treated, nulliparous rats, while NMA lesions in non-steroid-treated animals or vehicle infusions in steroid or non-steroid-treated rats failed to induce a rapid onset of behaviour. In a final study the effects of NMA lesions of the VMH were evaluated. As in AHA lesioned rats, NMA lesions of the VMH stimulated a fast onset of maternal behaviour in steroid-primed females. These findings indicate that the VMH as well as the DH/AHA exert chronic steroid-dependent inhibitory influences on the induction of maternal behaviour.

Null mutation of the prolactin receptor gene produces a defect in maternal behavior.

We have studied pup-directed maternal behavior in mice carrying a germ line null mutation of the PRL receptor (PRLR) gene. Homozygous mutant and heterozygous mutant nulliparous females show a deficiency in pup-induced maternal behavior. Moreover, primiparous heterozygous females exhibit a profound deficit in maternal care when challenged with foster pups. Morris maze studies revealed normal configural learning in the heterozygous and homozygous animals. Eating, locomotor activity, sexual behavior, and exploration (all processes regulated by the hypothalamus) are normal in PRLR mutant mice. Olfactory function was tested in an aversive conditioning paradigm, results indicating that heterozygous and homozygous PRLR mutant mice are not anosmic. These studies clearly establish the PRLR as a regulator of maternal behavior.

Reproductive experience and opioid regulation of luteinizing hormone release in female rats.

The objective of the present study was to determine whether reproductive experience that produces shifts in opioid regulation of prolactin secretion and behavioural functions also alters opioid regulation of LH during the oestrous cycle or lactation. In Expt 1 the effect of naloxone administration (i.v.) on LH was compared between age-matched, nulliparous and primiparous, catheterized female rats on dioestrus II. In Expt 2, the effects of multiple reproductive experiences on opiate control of LH were investigated using cyclic, nulliparous and multiparous (three litters) rats. In both experiments, no differences in naloxone-stimulated LH release were found between groups even though multiple reproductive experiences resulted in the prolongation of oestrous cyclicity. In Expt 3, day 8 lactating primiparous rats were administered 2, 5, 10 or 25 mg naloxone kg-1 i.v. The three lowest naloxone doses, but not the 25 mg kg-1 dose, significantly increased LH concentrations. The possible effects of prior reproductive experience on opioid control of LH during lactation were then investigated. Naloxone at 0.5 mg kg-1, but not at 2 mg kg-1 or 10 mg kg-1, stimulated a significantly greater rise in LH in multiparous (two litters) than in primiparous females. Overall, these data indicate that while modest differences were found in naloxone-induced LH responses between multiparous and primiparous animals during lactation, reproductive experience did not significantly alter opioid regulation of LH during subsequent oestrous cycles at the naloxone doses examined. Hence, the effects of reproductive experience on opioid regulation of LH are less pronounced than those previously found for opioid regulation of prolactin and behaviour.

Reproductive experience reduces haloperidol-induced prolactin secretion in female rats.

The present study examined possible changes in the dopaminergic regulation of prolactin (PRL) secretion which have been reported to occur in reproductively experienced female rats. In the first experiment, female rats which had raised a litter to weaning and age-matched nulliparous controls were ovariectomized and challenged sequentially 2 days apart with a low (0.2 mg/kg) and high (1.0 mg/kg) dose (intravenously) of haloperidol (HAL), a dopamine antagonist. Blood samples were collected via intra-atrial catheters, and plasma samples were assayed for PRL content by radioimmunoassay. Whereas HAL stimulated increases in plasma PRL concentrations in both nulliparous and primiparous animals, significantly higher levels of plasma PRL were present after both doses of HAL in the nulliparous rats. A second experiment investigated the role of lactation in this change in the ability of HAL to stimulate increases in circulating PRL levels. Separate sets of age-matched primiparous (pups removed on day 1 of lactation) and nulliparous rats were challenged with two doses of HAL 2 weeks after gonadectomy. In contrast to the effect of pregnancy and lactation found in the first experiment, pregnancy and parturition in the absence of lactation failed to alter the female's sensitivity to HAL. The PRL responses in the two groups were identical at the low HAL dose and similar after the high HAL dose. These findings demonstrate that a single prior pregnancy and lactation, but not pregnancy alone, significantly reduce the ability of HAL to elevate circulating plasma PRL concentrations. Decreased circulating PRL levels in reproductively experienced females, therefore, may result in part from increased endogenous dopaminergic activity/tone.

Suppression of testosterone and estradiol-17beta-induced dysplasia in the dorsolateral prostate of Noble rats by bromocriptine.

We, and others, have previously described the histological changes that occur in the prostate gland of intact Noble (NBL) rats following prolonged hormonal treatment. Dysplasia, a pre-neoplastic lesion, develops specifically in the dorsolateral prostates (DLPs) of NBL rats treated for 16 weeks with a combined regimen of testosterone (T) and estradiol-17beta (E2) (T + E2-treated rats). Concurrent with DLP dysplasia induction, the dual hormone regimen also elicits hyperprolactinemia, in addition to an elevation of nuclear type II estrogen binding sites (type II EBS), no alteration in estrogen receptors (ER), and marked epithelial cell proliferation in the dysplastic foci. The aim of this study was to investigate whether the dual hormone action is mediated via E2-induced hyperprolactinemia. Bromocriptine (Br), at a dose of 4 mg/kg body wt per day, was used to suppress pituitary prolactin (PRL) release. Serum PRL levels were lowered from values of 341 +/- 50 ng/ml in T + E2-treated rats to 32 +/- 10 ng/ml in Br co-treated animals. The latter values were comparable to those in untreated control rats. In addition, Br co-treatment effectively inhibited the evolution of dysplasia (six out of eight rats) and the often associated inflammation (five out of eight rats) in most animals. In contrast, Br co-treatment did not suppress the T + E2-induced type II EBS elevation nor alter ER levels in the DLPs of these rats, when compared with T + E2-treated rats. These data extend the many previous studies that have detailed marked influences of PRL on rat prostatic functions. However, the current study is the first to implicate PRL in prostatic dysplasia induction in vivo.

N-methyl-DL-aspartic acid lesions of the medial preoptic area disrupt ongoing parental behavior in male rats.

The effects of axon-sparing, neurotoxic lesions of the medial preoptic area (MPOA) with N-methyl-DL-aspartic acid (NMA) on previously established parental behavior in male rats were investigated. Adult, sexually-inexperienced male rats were gonadectomized and seven days later implanted sc with a single estradiol (E2)-filled Silastic capsule on treatment Day 1. Three progesterone (P4) capsules were implanted sc on treatment Day 3 and removed on Day 21, one day prior to the start of behavioral testing. Males were tested daily with foster pups in order to induce parental behavior, i.e., contacting the test pups, pup retrieval, grouping, and crouching over three foster pups. Full parental behavior appeared in these males after an average of 3 days. After testing on the third consecutive day of parental behavior, parental males were infused bilaterally with either NMA or vehicle into the MPOA. NMA infusions resulted in a significant decline in all components of parental behavior by the next test session, a deficit which persisted throughout the 5 days of post-infusion testing. In contrast, parental care continued to be displayed in animals given vehicle infusions. These findings demonstrate that the cells in the MPOA play an important role in regulating ongoing parental care in male rats and indicate that the neural substrates controlling parental behavior in male and female rats are similar.