The long lasting effects of electrical simulation of the medial preoptic area and medial amygdala on maternal behavior in female rats.

A program of repeated electrical (kindling-like) stimulation of the medial preoptic area (MPOA) or the medial amygdala (MedAmyg) on maternal and other behaviors were investigated. Stimulation was applied daily for 14 days (or until a stage 3 motor seizure was observed) using 2 s trains of biphasic square wave pulses at 60 Hz, 1 ms duration and 300-500 microA. Confirmation of afterdischarge using these parametres was established. In the first experiment, maternally experienced (but not post-partum) MedAmyg stimulated animals became maternal more slowly than did MedAmyg not stimulated animals or than MPOA stimulated animals. In the second experiment, virgin animals were used. MPOA stimulation enhanced the female's preference for pup associated environments in the conditioned place preference (CPP) paradigm. MedAmyg stimulation had no effect on CPP performance, but produced a decreased preference for pup odors in a modified hole board test and increased 'anxiety' in the open field. These results confirm that the MPOA and the MedAmyg are involved in facilitating and attenuating maternal responsiveness and related (precursor?) behaviors, respectively. It appears that chronic (kindling-like) stimulation of these neural substrates enhances their functions.     

Parity-associated alterations of medial preoptic opiate receptors in female rats.

Preoptic area opiate receptor density was measured by quantitative autoradiography using [3H]naloxone in female rats during their first and second pregnancies and lactations and in a separate group of ovariectomized, nulliparous animals. Opiate receptor density in the medial preoptic area (MPOA) was elevated on day 12 of gestation in both primigravid and multigravid rats when compared with ovariectomized subjects. MPOA receptor density was reduced in primiparous mothers on day 5 of lactation relative to pregnancy. In contrast, receptor density in the MPOA did not decline in multiparous (second lactation) rats relative to pregnancy levels. Opiate receptor density was significantly higher on day 5 of lactation in multiparous than in primiparous mothers. No difference in receptor density was detected in the adjacent lateral preoptic area among the treatment groups. An examination of hormone titers revealed that basal prolactin levels were significantly higher in primigravid than multigravid rats, and that during lactation prolactin titers were negatively correlated with MPOA opiate receptor density in the primiparous mothers. The data demonstrate that multiple pregnancies and lactations result in changes of MPOA opiate receptor density and of circulating hormone levels. The findings are discussed in terms of the concurrent changes in neural opiate sensitivity associated with multiparity.     

Neonatal handling reduces angiotensin II receptor density in the medial preoptic area and paraventricular nucleus but not in arcuate nucleus and locus coeruleus of female rats

Neonatal handling alters the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonads axis (HPG) in adult animals, and angiotensin II (Ang II) modulates the functions in these axes. We tested whether neonatal handling could change the density of Ang II receptors in some central areas in female rats. Results showed decreased density of the Ang II receptors in the medial preoptic area (MPOA) and hypothalamic paraventricular nucleus (PVN) of the neonatal handled group.     

Activity of monoamine oxidase in the medial preoptic area and median eminence of female rats of different ages

Total monoamine oxidase activity in the medial preoptic area and median eminence (with surrounding tissue) has been studied in female rats of three age groups, viz., those aged 1.5–2 months (peripubertal), 4–5 months (mature), and over 12 months (aging). Monoamine oxidase activity was measured using kynuramine as a substrate and changes in the concentration of product (4-hydroxyquinoline) were recorded at 327 nm. In the medial preoptic area, the lowest activity (nmole kynuramine/min/mg protein, M ± m) was found during the peripubertal period (1.55 ± 0.11), while in mature and aging rats the activities were similar (1.93 ± 0.12 and 2.01 ± 0.15, respectively). In the median eminence, the greatest activity of monoamine oxidase was found in the aging rats (6.61± 0.56), whereas in the rats of peripubertal and mature age the activities were similar (4.79 ± 0.57 and 4.36 ± 0.25, respectively). In animals aged 4–5 months, we found a tendency toward a negative correlation between the activity of monoamine oxidase in the medial preoptic area and the activity in the median eminence. Our results suggest that opposing changes in enzyme activity are necessary for the coordinated work of the monoaminergic systems in the areas studied.     

Axon sparing lesions of the medial preoptic area block female sexual behavior

The role of the medial preoptic area (mPOA) in regulating female musk shrew sexual behavior was assessed with excitatory neurotoxin, N-methyl-

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-aspartate (NMDA) lesions. Ovariectomized, testosterone-implanted females that received lesions in the mPOA were statistically less likely to show complete sex behavior as compared to controls. These data suggest that the mPOA plays an activational role in testosterone-induced female sexual behavior.     

Steroid implants in the medial preoptic area or ventromedial nucleus of the hypothalamus activate female sexual behaviour in the musk shrew

Female musk shrews are induced ovulators that do not exhibit a spontaneous behavioural oestrous cycle. Testosterone produced by the ovaries and adrenal glands, is the major steroid hormone in circulation at times of mating, and as such, regulates sexual behaviour. In the first experiment, we identified the neural site(s) of action for testosterone. Hormone implants were placed in one of three targeted brain regions. The neural sites selected were the medial anterior division of the bed nucleus of the stria terminalis (BNSTMA), medial preoptic area (mPOA) and the ventromedial nucleus of the hypothalamus (VMN). Ovariectomized females who received a unilateral testosterone propionate implant in either the mPOA or VMN, were significantly more likely to display sexual behaviour as compared to females who received an implant in the BNSTMA or any other hypothalamic nucleus. In experiments 2 and 3, we investigated whether the behavioural effects of testosterone propionate were mediated by an oestrogen receptor or the androgen receptor. Ovariectomized females that received oestradiol (E2) implants in either the mPOA or VMN were more likely to display receptivity, and had significantly shorter behavioural latencies, as compared to females implanted with either dihydrotestosterone or cholesterol. These data show that neural aromatization of testosterone to E2 in the mPOA or VMN is necessary for optimal activation of female musk shrew sexual behaviour. This finding implies a degree of neural redundancy in the networks that control the expression of sexual receptivity.     

Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats

The sexually dimorphic nucleus of the rat medial preoptic area (SDN-POA) has a volume five times larger in the adult male compared with that of the adult female. In the present study, the effects of discrete electrolytic destruction of the SDN-POA or other specific medial preoptic (MPOA) regions on masculine sexual behavior were determined in adult, sexually experienced male rats. Small lesions encompassing the SDN-POA had no effect on the maintenance of copulatory behavior. Lesions of similar size placed within the ventral or anterio-dorsal MPOA also did not consistently affect the display of masculine sexual behavior. However, animals that received small lesions within their dorsal MPOA showed a substantial, long-term decrease in number of mounts, intromissions, and ejaculations compared to these parameters in sham-lesioned control rats, thus indicating a lesion-induced disruption of those neural mechanisms mediating these behaviors. Collectively these data suggest that the SDN-POA is not critical for a full expression of male sexual behavior and that the dorsal MPOA may be more important than other MPOA regions for copulatory behavior.     

Morphine and dynorphin(1-13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats

The effects on sexual behavior of opiate receptor stimulation within A10 and A14 terminal areas were examined in the following experiments. Morphine (0.01-6 nmol) and dynorphin(1-13) (0.01-3 pmol) were microinjected into the medial preoptic area (MPOA). Morphine (10-100 pmol) and dynorphin (10-100 fmol) injected into the MPOA reduced both the latency to ejaculate and the number of intromissions triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating following the second ejaculation. Morphine (1-10 nmol) injected into the nucleus accumbens (ACC) shortened the latency to the first intromission and lengthened the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects of morphine on intromission latency and attenuated the lowering of ejaculatory threshold.     

Cyclic and age-related changes in norepinephrine concentrations in the medial preoptic area and arcuate nucleus

High-performance liquid chromatography with electrochemical detection (HPLC-EC) and Palkovits' microdissection technique were used to measure norepinephrine (NE) concentrations in the medial preoptic area (MPA) and arcuate nucleus (AN) during various stages of the estrous cycle. NE was measured seven times at 2-h intervals between 1000 h and 2200 h on the days of proestrus and diestrus in young (4-month-old) rats and four times at 2-h intervals between 1400 h and 2000 h in old (20–22-month-old) persistently diestrous rats. On the day of proestrus in young animals, NE increased progressively from low levels at 1000 h to peak levels at 2000 h, followed by a sharp decline at 2200 h. In contrast, no changes in NE occurred on the day of diestrus. Unlike the young proestrous rats, but similar to the young diestrous rats, no changes in NE concentrations either in the MPA or in the AN occurred in the old persistently diestrous rats. These data demonstrate that NE concentrations in the MPA and AN change during the estrous cycle. We believe the increase in NE on the aftemoon of proestrus is related to the surge in serum luteinizing hormone (LH) that occurs simultaneously in this stage of the estrous cycle. The lack of change in NE concentrations in the young diestrous and persistently diestrous old animals is consistent with the well-established absence of changes in serum LH in these animals.     

Perinatal androgenization prevents age-related neuron loss in the sexually dimorphic nucleus of the preoptic area in female rats

To investigate the effect of perinatal testosterone exposure, which simulates the endogenous testosterone peak, on neuron loss during aging, nuclear morphology was evaluated in male and female rats as well as in female rats treated with testosterone perinatally followed by ovariectomy (TE/Ovx). Additionally, neuronal apoptosis, which occurred primarily at postnatal day 8 (PND8), was identified by in situ TUNEL staining. Neuronal density, nuclear volume, total neuronal number and pyknotic ratio were estimated after HE stain at PND8, middle age and old age. The results showed that age-related decrease in neuronal nuclear volume and total neuron number in the sexually dimorphic nucleus of the preoptic area (SDN-POA) of female rats was significantly diminished by TE/Ovx. The pyknotic ratio in the SDN-POA of female rats at PND8 was significantly higher than that of males, and neuronal death was reversed by testosterone exposure, while no significant difference of pyknotic ratios was observed among male, female and TE/Ovx female rats at both middle and old age. Moreover, the high apoptotic incidence of female rats at PND8 was significantly diminished by testosterone exposure. These results suggest that neuron loss in the SDN-POA during aging may be predominantly determined by perinatal testosterone through modulation of postnatal neuronal apoptosis.     

Fast neurotransmission in the rat medial preoptic nucleus

The functional properties of neurotransmission in the medial preoptic nucleus (MPN) were studied in a brain slice preparation from young male rats. The aims were to evaluate the thin slice preparation for studying evoked synaptic responses in MPN neurons, to characterize the fast responses triggered by activation of presynaptic nerve fibers in the MPN, and to identify the involved receptor types. Presynaptic stimulation within the MPN evoked postsynaptic voltage and current responses that were blocked by 200 microM Cd2+ or by 2.0 microM tetrodotoxin and were attributed to action potential-evoked transmitter release. The relation to stimulus strength and comparison with spontaneous synaptic currents suggested that in many cases only one presynaptic nerve fiber was excited by the stimulus. Furthermore, the transmission was probabilistic in nature, with frequent failures. Thus, response probability, most likely reflecting transmitter release probability, could be evaluated in the thin slice preparation. Evoked excitatory postsynaptic currents recorded under voltage-clamp conditions were, due to kinetics, I-V relation, and pharmacological properties, attributed to AMPA/kainate receptors and NMDA receptors, whereas inhibitory currents were attributed to GABAA receptors. No responses that could be attributed to glycine or other types of primary transmitters were detected. Although serotonin (5-HT) did not appear to function as a primary transmitter, glutamate- as well as GABA-mediated transmission was suppressed by 500 microM 5-HT, with a clear reduction in response probability observed. 5-HT also reduced the frequency, but not the amplitude, of spontaneous postsynaptic currents and was therefore ascribed a presynaptic site of action.     

Lordosis-enhancing medial preoptic area lesions do not alter hypothalamic estrogen receptor- or progestin receptor-immunoreactivity in prepubertal female guinea pigs

Female guinea pigs rarely display adult-typical lordosis responses to ovarian steroid hormones until 40–50 days of age. Behavioral hyporesponsiveness in prepubertal females may be due, in part, to deficiencies in hypothalamic estrogen receptors and/or estradiol-induced progestin receptors. This study was designed to test the hypothesis that bilateral medial preoptic area (MPOA) lesions, which enhance the display of progesterone-facilitated lordosis in juvenile females, increase levels of hypothalamic estrogen receptors and/or estradiol-induced progestin receptors. Hartley guinea pigs were ovariectomized at 11–12 days of age and at 14–15 days of age received bilateral electrolytic or sham lesions aimed at the MPOA. At approximately 3 weeks of age, lesioned and sham-lesioned animals were either tested for the display of progesterone-facilitated lordosis or perfused, and their hypothalamic tissue processed for estrogen receptor- or estradiol-induced progestin receptor-immunostaining. Although a significantly higher percentage of MPOA-lesioned than sham-lesioned guinea pigs displayed progesterone-facilitated lordosis (85.7% vs. 5.8%, respectively, p<0.05), there were no significant lesion-related differences in the number or staining intensity of cells containing estrogen receptor- or estradiol-induced progestin receptor-immunoreactivity in the ventrolateral hypothalamus or arcuate nucleus. These data do not support the hypothesis that the enhanced display of progesterone-facilitated lordosis in prepubertal guinea pigs following MPOA lesions is due to increased hypothalamic concentrations of estrogen receptors or estradiol-induced progestin receptors.     

Efferent projections of the medial preoptic nucleus and medial hypothalamus in the pigeon

The efferent projections of the medial preoptic nucleus (POM), anterior-medial hypothalamic area (AM), and the posteromedial hypothalamic nucleus (PMH) in the pigeon were traced by the autoradiographic technique. Similar and differential connections were noted from these regions. Projections from POM and AM-PMH were traced to nucleus septalis lateralis, nucleus dorsomedialis thalami, nucleus dorsolateralis anterior thalami (pars ventralis), posterior hypothalamic and medial mammillary areas, area ventralis tegmenti (Tsai), central gray of midbrain and nucleus intercollicularis and substantia grisea periventricularis of the midbrain. The density of silver grains in these regions differed with POM and AM-PMH injections. Other projections were observed exclusively from only one or two of the nuclear regions injected. Connections from POM and the rostral part of AM were seen to the median eminence, neurohypophysis, and the nucleus of anterior pallial commissure. Only cells of the anterior part of AM project fibers to nucleus septalis medialis. In the hypothalamus, projections from POM are concentrated in the periventricular region and in the preoptic-hypophyseal tract in the extreme lateral hypothalamus, while AM-PMH projections are heaviest in the medial hypothalamus and lateral preoptic area. A major difference in the connections of PMH from POM is the more substantial PMH projection to the midbrain. A prominent projection courses dorsolaterally and posteriorly from PMH toward nucleus ovoidalis and splits into two pathways: a lateral pathway which heavily innervates n. intercollicularis and the periventricular gray and a ventrolateral projection to the midbrain tegmentum. The projections described above provide anatomical substrates for neuroendocrine, autonomic, and behavioral functions.     

Ibotenic acid lesions of the medial preoptic area disrupt the expression of partner preference in sexually receptive female rats

The present study evaluated the effects of ibotenic acid lesions of the medial preoptic area (mPOA) on the display of partner preference in ovariectomized, estrogen- and progesterone-primed rats. Preference for a sexually vigorous male or an estrous female rat was determined in one of two conditions: unlimited physical access to the stimulus rats (Contact condition) or access that was limited to olfactory, auditory and visual cues (No-contact condition). Lesions of the mPOA reduced the male preference, social preference, and arena crossings, independent of test condition. However, the reduction in male preference following mPOA lesions was most pronounced during tests with unlimited physical access. These results suggest that the mPOA may be involved in integrating somatosensory signals from coital stimulation with the motor responses associated with the appetitive aspects of female sexual behavior.     

Effects of small medial preoptic lesions on estrous cycles and receptivity in female rats

The effects of small lesions in the preoptic area (POA) of female rats on estrous cycles, LH responsiveness, and receptivity were studied. Regularly cycling rats received lesions confined to either the periventricular portion or the ventral portion of the rostral preoptic area, or a combination of these two sites. Nine animals showed persistent vaginal cornification (PVC) following lesion placement. All of these had lesions in the periventricular preoptic area. In contrast, five of six animals which showed repeated periods of pseudopregnancy (RPP) had lesions in the most ventral portion of the preoptic area. Lesions which damaged both the periventricular POA and the ventral POA gave mixed results. Following ovariectomy and estrogen and progesterone stimulation, the RPP animals had higher levels of LH 6 hr after the P injection than did the control animals or PVC animals. In three different tests for female sexual behavior-with estrogen alone, estrogen plus progesterone, and low estrogen priming and repetitive sexual stimulation-the PVC animals had consistently lower receptivity than the controls. The RPP animals were more receptive than the controls in all but the estrogen plus progesterone tests. The decreased levels of receptivity of the PVC animals could be related to a disruption of the LHRH system, while the RPP group responses could reflect a hypersensitivity of remaining neurons to estrogen.     

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.     

Morphine and dynorphin(1–13) microinjected into the medial preoptic area and nucleus accumbens: effects on sexual behavior in male rats

The effects on sexual behavior of opiate receptor stimulation within A10 and A14 terminal areas were examined in the following experiments. Morphine (0.01–6 nmol) and dynorphin(1–13) (0.01–3 pmol) were microinjected into the medial preoptic area (MPOA). Morphine (10–100 pmol) and dynorphin (10–100 fmol) injected into the MPOA reduced both the latency to ejaculate and the number of intromissions triggering ejaculation. Morphine (6 nmol) produced a failure to resume copulating following the second ejaculation. Morphine (1–10 nmol) injected into the nucleus accumbens (ACC) shortened the latency to the first intromission and lengthened the second postejaculatory interval. Naloxone (3 mg/kg i.p.) reversed the effects of morphine on intromission latency and attenuated the lowering of ejaculatory threshold.     

Interrelationship of thermal and sleep-wakefulness changes elicited from the medial preoptic area in rats

The study investigated the possible interrelationship between changes in sleep-wakefulness and body temperature, primarily induced by manipulation of the noradrenergic system in the medial preoptic area. Saline, norepinephrine, and its alpha- and beta-blockers were injected in the medial preoptic area and in some control areas of rats, during their sleeping and active periods. 5-Hydroxytryptamine was injected in the medial preoptic area in another group of animals. Simultaneous changes in sleep-wakefulness and the body temperature were continuously recorded. Norepinephrine produced hypothermia and arousal, whereas alpha-adrenergic blockers induced hyperthermia and sleep. These changes in body temperature and in sleep-wakefulness did not follow an identical time course. 5-Hydroxytryptamine induced hyperthermia without affecting sleep-wakefulness. It is suggested that there are different neuronal mechanisms in the medial preoptic area that bring about the drug-induced changes in temperature and sleep-wakefulness.     

Alpha adrenergic system in medial preoptic area involved in sleep-wakefulness in rats

The study is aimed at investigating the possible involvement of adrenergic mechanisms in the medial preoptic area (mPOA) for modulation of sleep-wakefulness in rats. In this study, saline, norepinephrine (NE), phenoxybenzamine (PBZ) and propranolol (PROP) were injected in the mPOA in different groups of male rats during the day and night. NE and PBZ were injected, during the day and the night respectively, in some control areas adjoining the mPOA in two other groups of animals. Arousal was produced by NE, and sleep by PBZ when they were applied in the mPOA. All other procedures, including application of NE and PBZ in the control areas and beta blocker (PROP) in the mPOA, did not produce alterations in sleep-wakefulness. These findings provide support for a physiological role played by the alpha adrenergic system in the mPOA for arousal, and area specificity of action of this system.