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Biomedical subjects

R S Bridges

Publications and source records attributed to R S Bridges.

At least 19 recordsLinked to original sources
PubMed2001

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.

Animals↗
PubMed2001

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.

Animals↗
PubMed2001

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.

Brain↗
PubMed2000

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.

Age Factors↗
PubMed2000

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.

Animals↗
PubMed1999

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.

Analysis of Variance↗
PubMed1999

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.

Animals↗
PubMed1998

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.

Animals↗
PubMed1998

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.

Analysis of Variance↗
PubMed1997

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.

Animals↗
PubMed1997

Differential proopiomelanocortin gene expression in the medial basal hypothalamus of rats during pregnancy and lactation.

Hypothalamic proopiomelanocortin (POMC) gene expression was determined using in situ hybridization histochemistry (ISHH) during pregnancy and lactation in rats with and without prior reproduction experience. POMC mRNA levels in the arcuate nucleus were compared between primigravid (first pregnancy) and multigravid (second pregnancy) and primiparous and multiparous lactating rats, and between these groups and age-matched, regularly cycling, nulliparous females in diestrus. Hybridizations were performed using a digoxigenin-labeled riboprobe complementary to 837 bp of the POMC gene. The number of cells expressing POMC mRNA in the arcuate nucleus decreased in primiparous rats on day 12 of lactation when compared with the number of POMC cells in the arcuate nucleus of nulliparous rats in diestrus. In addition, the number of cells expressing POMC mRNA in multigravid animals was significantly less than in the primigravid group on days 7 and 21 of pregnancy, and on day 12 of lactation in primiparous animals. Repeated reproductive experience affected the number of POMC mRNA positive cells; there were fewer cells expressing POMC mRNA in the multigravid females on day 7 of pregnancy and an increase in the number of POMC cells in the multiparous group on day 12 of lactation compared to the primiparous animals. Optical density measurements revealed a significant increase in reaction product in the labeled cells on all days of pregnancy compared with virgin females in diestrus and a significant decrease in reaction product on day 12 of lactation in the multiparous group. The results of the present study indicate that POMC gene expression changes across pregnancy and lactation and that repeated reproductive experience has long-term, possibly permanent, effects on the endogenous opioid system.

Analysis of Variance↗
PubMed1997

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.

Animals↗
PubMed1997

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.

Analysis of Variance↗
PubMed1997

Central lactogenic regulation of maternal behavior in rats: steroid dependence, hormone specificity, and behavioral potencies of rat prolactin and rat placental lactogen I.

Adult virgin female rats display maternal behavior when continuously exposed to foster young for 5-6 days. Central infusions of PRL or placental lactogens (PLs) together with systemic treatment of progesterone (P) and estradiol (E2) stimulate maternal behavior in 1-2 days. In the present set of studies, it was asked whether the actions of lactogenic hormones are dependent upon both E2 and P and specific to lactogenic molecules. Moreover, we wanted to know whether central infusions of rat (r) PRL and PLs were equally effective in inducing maternal behavior. In the first study, adult virgin rats were ovariectomized (ovx) and stereotaxically fitted with bilateral cannulas directed at the medial preoptic area (MPOA). Rats were then assigned to one of four groups: P plus E2, blank (B) plus E2, P plus B, and B plus B. P-filled or B capsules were implanted sc on treatment day 1 and removed on day 11, whereas E2 or B capsules were implanted on day 11. All groups were infused with rPRL (40 ng/side) five times from days 11-13 and injected with bromocriptine (CB-154) sc (days 11-17) to suppress endogenous PRL release. Behavioral testing was conducted daily from days 12-17. It was found that exposure to both P and E2 was necessary to induce a fast onset of maternal behavior in PRL-infused females; priming with P or E2 alone in PRL-treated rats failed to stimulate a fast onset of behavior relative to that in nonsteroid-treated controls. In the second experiment to determine the biochemical specificity of PRL's action, adult nulliparous rats were ovx, implanted with bilateral cannulas directed at the MPOA, treated with both P and E2, injected with CB-154, and infused centrally (five times) with 40 ng (per side) of bovine GH, ovine LH, or vehicle. Central infusions of either bovine GH or ovine LH failed to stimulate maternal behavior, suggesting that the stimulatory actions of PRL are related to its lactogenic properties. In the final study, rats were ovx, fitted with bilateral cannulas directed at the MPOA; treated with P, E2, and CB-154; and given a single set of bilateral infusions of rPL-I or rPRL (40 ng/side.infusion) on day 11, three sets of infusions of rPL-I or rPRL (days 11 and 12), or vehicle infusions. Rats given three infusions of rPL-I and rPRL responded faster than controls, although the effect was not as robust as that in animals given five infusions in the initial study. rPL-I and rPRL groups did not differ from one another. Together these studies indicate that 1) both P and E2 are required for lactogenic stimulation of maternal behavior; 2) the stimulatory actions of PRL and rPLs on maternal behavior are related to their lactogenic properties; 3) extended treatment of females with lactogenic hormones is more effective in stimulating the onset of maternal behavior; and 4) the neural potencies of rPRL and rPL-I are similar. These findings provide support for the idea that the induction of maternal behavior is stimulated by the central actions of lactogenic hormones.

Animals↗
PubMed1996

Inhibitory effects of naltrexone on the induction of parental behavior in juvenile rats.

Juvenile rats are rapidly responsive to pups soon after weaning, displaying maternal-like behaviors such as licking, retrieving, grouping, and crouching over pups. As juveniles reach 30 days of age, they become less responsive to pups and show increased latencies to display the same parental behaviors. In light of previous data implicating opiates in the display of ongoing maternal behavior, we administered naltrexone, a long-acting opiate antagonist, beginning 5 and 9 days prior to and continuing throughout the period of behavioral testing, which started at 26 or 30 days of age. Male and female juveniles treated with 10 mg/kg of naltrexone SC for 9 days (days 21 to 29 of age) prior to and during behavioral testing (days 30 to 37) showed longer latencies to retrieve, group, and crouch over pups than did the vehicle-injected controls. These results suggest that opioids may have a stimulatory role in parental behavior during this prepubertal period.

Aging↗
PubMed1996

Reproductive experience increases striatal and hypothalamic dopamine levels in pregnant rats.

The effects of parity on the dopaminergic function of rats were studied. Striatal and hypothalamic levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) as well as serum prolactin (PRL) levels of 7-days primigravid and multigravid rats were compared. Brains and trunk blood were collected from 1200-1400 h on day 7 of pregnancy and assayed for monoamines and their metabolites, and prolactin, respectively. Multigravid rats showed a significant increase in striatal and hypothalamic dopamine levels. A tendency to increase in striatal DOPAC levels was also observed in multigravid rats. Levels of other neuro-transmitters and metabolites were not statistically different. Haloperidol (1 mg/kg) treatment induced a significant increase in multigravid 5-HT striatal levels. There was no statistical difference among primigravid and multigravid serum PRL levels after either saline or haloperidol treatment. These data suggest that prior parity produces a shift in dopaminergic activity in multigravid rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Endocrine communication between conceptus and mother: placental lactogen stimulation of maternal behavior.

The possible role of the conceptus in stimulating the onset of maternal behavior through its secretion of placental lactogens and their passage into the brain was investigated in female rats. In the first study, significant mitogenic activity in the Nb2 lymphoma cell bioassay was detected in cerebrospinal fluid (CSF) samples collected by push-pull perfusion from rats on days 12-21 of pregnancy, coincident with the establishment of placental function. In contrast, mitogenic activity was absent from CSF in lactating and gonadectomized, virgin females. In a second study the mitogenic activity in day 12 pregnant samples was neutralized 71% with antibodies to rat placental lactogen-I (rPL-I) and > 90% with a combination of antibodies to rPL-I plus rPL-II. In contrast, activity on day 21 of pregnancy, 1 day prepartum, was reduced by antibodies to rPL-II (> 85%), but not by antibodies to rPL-I, indicating that the predominant lactogen in the CSF prepartum is rPL-II. The behavioral actions of placental secretions were assessed in the third experiment by infusing recombinant rPL-I and purified rPL-II directly into the medial preoptic area of the brain of steroid-primed, nulliparous rats. Latencies to respond maternally to foster young were significantly reduced in rPL-I- and rPL-II-treated rats (2- to 3-day latencies) when compared with latencies in control females (5- to 6-day latencies). Thus, the conceptus through its secretion of rPLs which apparently gain access to the CSF helps to prime the pregnant female's brain to respond maternally at the end of gestation. This endocrine communication between the developing conceptus and pregnant female appears to be an important part of the biological system which helps to establish successful maternal care.

Animals↗