Medial Preoptic Anterior Hypothalamus Research Articles

Response of medial preoptic/anterior hypothalamic neurones to ventrolateral medulla stimulation and its attenuation by adrenoceptor antagonists.

Extracellular single-unit recordings were made from medial preoptic/anterior hypothalamic (MPOAH) neurones in urethane-anaesthetized female rats, and the responses of these neurones to electrical stimulation of the ventrolateral medulla (VLM) were investigated. Of 189 neurones tested, 20% were excited and 21% were inhibited following VLM stimulation. The latency of inhibitory responses showed a normal distribution and the mean latency was 47 ms, whereas the latency of excitatory responses showed a bimodal distribution with peaks in the ranges of 0-10 ms and 40-50 ms, respectively. Excitatory responses with latencies greater than 15 ms and inhibitory responses were significantly attenuated by intravenous injections of the alpha-adrenoceptor antagonist phenoxybenzamine but not the beta-adrenoceptor antagonist propranolol. In the light of these observations and the known anatomical and electrophysiological findings, it is suggested that A1 noradrenergic and/or C1 adrenergic inputs from the VLM to MPOAH neurones are, at least in part, mediated by alpha-adrenoceptors.

A sexually dimorphic hypothalamic nucleus in a macaque species with frequent female–female mounting and same-sex sexual partner preference

In some captive and free-ranging populations, unmanipulated female Japanese macaques ( Macaca fuscata) routinely court, mount (with pelvic thrusting), compete for, and even prefer, on occasion, certain female sexual partners over certain males. The goal of this study was to determine if the cytoarchitecture of the dorsocentral portion of the anterior hypothalamic nucleus (AHdc), was male-typical in female Japanese macaques drawn from one such population. The AHdc is located in the medial preoptic anterior hypothalamus (MPO-AH), a region of the brain that is known to regulate sexual behaviour in primates. Despite their potential for male-typical sexual behaviour and sexual partner preference, our female subjects did not possess male-typical AHdc. The AHdc was significantly larger in males than it was in females, a difference that could be attributed to the significantly larger number of neurons in the male AHdc compared to that of the females. The AHdc of female Japanese macaques were no more male-typical in size than those of female rhesus macaques, a closely related sister species in which females rarely exhibit male-typical sexual behaviour. Although the AHdc may be involved in the regulation of sexual behaviour, this study indicates that a male-typical AHdc is not a prerequisite for the expression of male-typical sexual behaviour and sexual partner preference in Japanese macaques. This study is the first to examine the relationship between sex-atypical sexual activity and the cytoarchitecture of a hypothalamic nucleus in hormonally unmanipulated females.

Cellular observations and hormonal correlates of feedback control of luteinizing hormone secretion by testosterone in long-term castrated male rhesus monkeys.

Testosterone at physiological levels cannot exert negative feedback action on LH secretion in long-term castrated male monkeys. The cellular basis of this refractoriness is unknown. To study it, we compared two groups of male rhesus macaques: one group (group 1, n = 4) was castrated and immediately treated with testosterone for 30 days; the second group (group 2, n = 4) was castrated and treated with testosterone for 9 days beginning 21 days after castration. Feedback control of LH by testosterone in group 1 was normal, whereas insensitivity to its action was found in group 2. Using the endpoints of concentrations of aromatase activity (P450(AROM) messenger RNA [mRNA]) and androgen receptor mRNA in the medial preoptic anterior hypothalamus and in the medial basal hypothalamus, we found that aromatase activity in both of these tissues was significantly lower, P: < 0.01, in group 2 compared with group 1 males. P450(AROM) mRNA and androgen receptor mRNA did not differ, however. Our data suggest that the cellular basis of testosterone insensitivity after long-term castration may reside in the reduced capacity of specific brain areas to aromatize testosterone. Because P450(AROM) mRNA did not change in group 2 males, we hypothesize that an estrogen-dependent neural deficit, not involving the regulation of the P450(AROM) mRNA, occurs in long-term castrated monkeys.

Injection of Oxytocin into the Medial Preoptic–Anterior Hypothalamus Increases Ultrasound Production by Female Hamsters

Recent studies of hamsters have documented the facilitation of lordosis and other sociosexual responses by injections of oxytocin (OXT) into the medial preoptic area-anterior hypothalamus (MPOA-AH). These data suggest the regulation of social interaction and bonds by OXT. In turn, this suggests that OXT could act in the MPOA-AH to control other behaviors involved in the initiation or maintenance of social contact, including the ultrasonic vocalizations that female hamsters use to alert and attract potential mates. To test this possibility, we compared the ultrasound rates of 11 naturally estrous hamsters before and after injections of OXT (200 ng/200 nl of saline) or saline (200 nl) into the MPOA-AH. The data revealed a clear facilitation of ultrasound rate 30 min after OXT treatment. This result suggests the modulation of ultrasound rate by endogenous OXT acting within the MPOA-AH. It extends the range of social behaviors sensitive to control by OXT and supports the possibility that OXT acts within the MPOA-AH to facilitate a variety of behaviors involved in the establishment or maintenance of the social interactions required for successful reproduction. At the same time, these data extend earlier observations linking ultrasound production to the MPOA-AH, and begin to describe the peptidergic mechanisms controlling this form of reproductive behavior.

Oxytocin immunoreactivity in the hypothalamus of female hamsters

In Syrian hamsters (Mesocricetus auratus), oxytocin (OXT) activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays an important role in the expression of sexual receptivity. Immunocytochemical analysis with OXT-specific antibodies was used to identify the distribution of OXT-containing cell bodies and fibers in female hamster brain and to determine the possible sources of OXT important for sexual receptivity. Oxytocin-immunoreactive cell bodies and fibers were found in several regions of the preoptic area, including the medial preoptic area, the medial preoptic nucleus, and the bed nucleus of the stria terminalis. Large numbers of cell bodies and fibers were localized within the paraventricular and supraoptic nuclei, and in anterior hypothalamus. OXT-immunoreactive fibers were observed in the VMH and the ventral tegmental area. The anatomical data from the present study support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.

Role of the central amygdala in social communication in Syrian hamsters ( Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) controls a form of scent marking called flank marking. Microinjection and lesion studies have identified several components of the neural circuit controlling this behavior. Microinjection of AVP into the medial preoptic–anterior hypothalamus (MPOA-AH), lateral septal nucleus (LS), bed nucleus of stria terminalis (BNST), and periaqueductal gray (PAG) stimulates an intense bout of flank marking. Lesions of areas such as the MPOA-AH and the LS inhibit flank marking. Other studies employing Fos immunocytochemistry suggest that the central amygdala (Ce) might be a component of this neural circuit. The purpose of the present study was to assess the significance of the Ce in regulation of AVP-induced flank marking. In Expt. 1A, the Ce of hamsters were either lesioned with ibotenic acid or sham-lesioned. In Expt. 1B, the Ce of hamsters were either lesioned electrolytically or sham-lesioned. All lesions were made bilaterally. One week later, hamsters were microinjected with AVP into the MPOA-AH and immediately tested for flank marking. In Expt. 2, the hamsters were microinjected with AVP into the Ce and were immediately tested for flank marking. Ibotenic lesions of the Ce reduced flank marking and electrolytic lesions completely inhibited flank marking in response to AVP microinjected into the MPOA-AH. Sham-lesions or lesions placed in other areas of the amygdala resulted in intense bouts of AVP-induced flank marking and flank grooming. No flank marking or flank grooming was observed in response to AVP microinjected into the Ce. These data indicate that the Ce plays a critical role in AVP-induced flank marking, although flank marking is not induced by AVP within the Ce itself.

Glutamate and vasopressin interact to control scent marking in Syrian hamsters (Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH) controls a form of scent marking called flank marking. Another neurochemical signal that may interact with AVP to control flank marking is glutamate. We tested the hypothesis that glutamate interacts with AVP in the MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA-AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA antagonist, or GAMS, a non-NMDA antagonist or propranolol, a β norepinephrine antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high levels of marking in response to AVP alone or to a combination of AVP and propranolol. In contrast, the frequency of marking was significantly reduced in response to a combination of either AVP and AP-5 or AVP and GAMS. These data support the hypothesis that stimulation of flank marking by AVP within the MPOA-AH requires the activity of glutamate.

Glutamate and vasopressin interact to control scent marking in Syrian hamsters ( Mesocricetus auratus)

In Syrian hamsters, vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH) controls a form of scent marking called flank marking. Another neurochemical signal that may interact with AVP to control flank marking is glutamate. We tested the hypothesis that glutamate interacts with AVP in the MPOA-AH to regulate flank marking. On day 1, AVP was microinjected into the MPOA-AH. On day 2, AVP was microinjected as a cocktail combining either AP-5, a NMDA antagonist, or GAMS, a non-NMDA antagonist or propranolol, a β norepinephrine antagonist. On day 3, AVP alone was microinjected. Hamsters engaged in high levels of marking in response to AVP alone or to a combination of AVP and propranolol. In contrast, the frequency of marking was significantly reduced in response to a combination of either AVP and AP-5 or AVP and GAMS. These data support the hypothesis that stimulation of flank marking by AVP within the MPOA-AH requires the activity of glutamate.

Neural circuitry controlling vasopressin-stimulated scent marking in Syrian hamsters (Mesocricetus auratus)

In Syrian hamsters, arginine vasopressin (AVP) plays a critical role in the control of a form of scent marking called flank marking. Microinjection of AVP into the medial preoptic-anterior hypothalamus (MPOA-AH), lateral septal nucleus (LS), bed nucleus of the stria terminalis (BNST), and the periaqueductal gray (PAG) stimulates high levels of flank marking. Microinjection of an antagonist of the V1a-AVP receptor into sites such as the MPOA-AH inhibits expression of flank marking. The purpose of the present study was to investigate the neural circuit controlling flank marking by localizing the induction of Fos protein in response to the microinjection of AVP, a V1a-AVP antagonist (AVPA) or saline into the MPOA-AH. Immediately after microinjection, hamsters were placed in a clean cage and their behavior was videotaped for 10 minutes. Ninety minutes after the behavioral experiment hamsters were perfused and their brains removed for subsequent immunocytochemical localization of Fos protein. The number of Fos-positive neurons was significantly greater in the BNST, PAG, and central amygdala (Ce) following the microinjection of AVP than following the microinjection of either AVPA or saline. In AVP-injected animals, the number of Fos-labeled cells in the Ce, PVN, and PAG increased with increased frequency of either flank marking or flank gland grooming. These data support the hypothesis that neurons within the MPOA-AH, BNST, and PAG play an important role in the control of flank marking and suggest that the Ce may be a previously unrecognized part of this neural circuit.

Ovarian hormones alter the behavioral response of the medial preoptic anterior hypothalamus to arginine-vasopressin.

In Syrian hamsters (Mesocricetus auratus) arginine-vasopressin (AVP) within the medial preoptic-anterior hypothalamus (MPOA-AH) plays a critical role in the control of a hormone-dependent behavior called flank marking. The present study investigated whether ovarian hormones influence flank marking by altering the response of the MPOA-AH to AVP. The amount of flank marking stimulated by microinjection of AVP (9 microM in 200 nl saline) into the MPOA-AH varied significantly over the 4 days of the estrous cycle with the lowest levels of flank marking observed on estrus. A second experiment demonstrated that administration of progesterone significantly reduced AVP-stimulated flank marking in estradiol-treated ovariectomized hamsters. These data support the hypothesis that the changing levels of estradiol and progesterone during the estrous cycle influence flank marking by altering the sensitivity or response of the MPOA-AH to AVP.

Role of oxytocin in the hypothalamic regulation of sexual receptivity in hamsters

Oxytocin (OXT) has been implicated in the control of a variety of social and reproductive behaviors in several species. The purpose of the present study was to test the hypothesis that OXT activity within the medial preoptic-anterior hypothalamus (MPOA-AH) and the ventromedial hypothalamus (VMH) plays a critical role in the expression of sexual receptivity in Syrian hamsters. The first 2 experiments investigated whether OXT would stimulate sexual receptivity in female hamsters in a dose-dependent manner. A 3rd experiment investigated whether sexual receptivity would be inhibited when endogenous OXT activity was blocked. Microinjection of OXT into the MPOA-AH or the VMH induced sexual receptivity in a dose-dependent manner in ovariectomized (OVX) hamsters primed with estradiol. Microinjection of a selective OXT antagonist, d(CH 2) 5[Tyr(Me) 2Thr 4,Tyr-NH 29] ornithine vasotocin into the MPOA-AH or the VMH significantly reduced the levels of sexual receptivity exhibited by OVX hamsters administered estradiol and progesterone. These findings support the hypothesis that OXT activity in the MPOA-AH and the VMH plays an important role in the regulation of sexual receptivity in hamsters.

Estradiol increases the behavioral response to arginine vasopressin (AVP) in the medial preoptic-anterior hypothalamus

Flank marking, a form of hamster scent marking controlled by arginine vasopressin (AVP) in the medial preoptic-anterior hypothalamus (MPOA-AH), is altered by circulating levels of gonadal hormones. We hypothesized that gonadal hormones influence flank marking either by altering the availability of AVP for release in the MPOA-AH or by altering the sensitivity or responsiveness of MPOA-AH neurons to AVP. We examined the levels of AVP immunoreactivity (AVP-IR) over the estrous cycle in the MPOA-AH and other areas. Arginine vasopressin immunoreactivity did not vary in the areas examined as a function of the stage of the estrous cycle. In Experiment 2 we measured flank marking after MPOA-AH microinjection of AVP in ovariectomized hamsters receiving estradiol or empty Silastic capsules. Hamsters implanted with estradiol capsules marked significantly more in response to AVP than did hamsters receiving no hormone replacement. These results support the hypothesis that estradiol influences flank marking by altering the sensitivity or responsiveness of the MPOA-AH or its efferents to AVP. Additionally, we observed an unexpected effect of AVP in estradiol-treated hamsters. After microinjection with 90 μ M AVP, lordosis occurred spontaneously in 60% of the hamsters even though no male was present. We suggest that female hamsters may be a useful model to further investigate the role of AVP and AVP-like peptides in female sexual behavior.

Pathways linking the olfactory bulbs with the medial preoptic anterior hypothalamus are important for intermale aggression in mice

Manipulations affecting olfaction, as well as bilateral lesions of the medial preoptic anterior hypothalamic (MPAH) continuum, decrease intermale aggression in mice. In the present study, unilateral removal of an olfactory bulb was combined with a contralateral lesion of the MPAH. This surgery, like bulbectomy and bilateral lesions of the MPAH, substantially decreased aggressive behavior. This surgery bilaterally destroys the ipsilateral links between the olfactory bulbs and the MPAH, and it is this disruption that presumably causes the decrease in aggression. The effect is not due to removal of an olfactory bulb combined with hypothalamic damage per se, because ipsilaterally lesioned/bulbectomized males continued to fight without decrement after surgery. These results provide compelling evidence that multisynaptic neural pathways linking the chemosensory systems of the olfactory bulbs with the rostral hypothalamus are involved in the regulation of intermale aggression in mice.

Interleukin-1 beta acts at hypothalamic sites to inhibit gastric acid secretion in rats.

It has been established that interleukin-1 beta (IL-1 beta) injected into the cerebrospinal fluid inhibits gastric acid secretion in rats. Brain sites of action of IL-1 beta were investigated in conscious rats implanted unilaterally with chronic hypothalamic cannula. Gastric acid secretion was monitored 2 h after pylorus ligation. Human recombinant IL-1 beta (10 ng) microinjected into the medial preoptic area, anterior hypothalamus, and paraventricular nucleus inhibited gastric acid secretion by 76-83%. IL-1 beta microinjected into the ventromedial hypothalamus and other hypothalamic sites outside of responsive sites had no effect. IL-1 beta inhibitory action in the medial preoptic area was dose related (0.1-10 ng), prevented by indomethacin (5 mg/kg ip), and mimicked by prostaglandin E2. These results show that IL-1 beta acts in the medial preoptic area/anterior hypothalamus and paraventricular nucleus to inhibit acid secretion in pylorus-ligated rats and that IL-1 beta action is likely to involve prostaglandin E2.

D 2 dopamine receptor-mediated mechanisms in the medial preoptic-anterior hypothalamus regulate affective defense behavior in the cat

The role of the dopaminergic innervation of the medial preoptic-anterior hypothalamus (mPO-AH) in regulating the expression of affective defense behavior in the cat has been investigated in the present study. Feline affective defense behavior, characterized mainly by autonomic arousal, ear retraction, growling, hissing and paw striking, was elicited by electrical stimulation of the ventromedial hypothalamic nucleus (VMH). Following the establishment of a stable threshold current for eliciting the hissing response of the behavior, the effect of injecting various DAergic agonists and antagonists into the mPO-AH on the hissing threshold was determined. The microinjection of the non-selective DA agonist apomorphine (0.03, 0.16, 0.33, 0.66, 1.56 and 3.3 nmol) into the mPO-AH facilitated hissing in a time- and dose-dependent manner. This effect was mimicked by the D2-selective agonist LY 171555 (0.2 and 1.0 nmol) but not by the D1-selective agonist SKF 38393 (1.7 and 17 nmol), and was blocked by the non-selective and the D2-selective antagonists haloperidol (1.3 nmol) and sulpiride (14.5 nmol), respectively. The injection of the D1-selective antagonist SCH 23390 (0.3 nmol), however, did not inhibit apomorphine-induced facilitation of hissing. In addition, the injection of haloperidol (1.3 nmol) and sulpiride (14.5 nmol), but not SCH 23390 (0.3 nmol), alone inhibited the behavior. It was therefore concluded that dopaminergic stimulation of the mPO-AH may facilitate the expression of affective defense behavior in the cat via a D2 receptor-mediated mechanism. The physiological significance of this effect and the interaction between dopaminergic, noradrenergic and serotonergic innervation of the mPO-AH in modulating the expression of affective defense behavior in response to threatening stimuli are discussed.

Comparative neuroanatomy of the sexually dimorphic hypothalamus in monogamous and polygamous voles

In the present work we evaluated the degree of sexual dimorphism in two cell groups of the medial preoptic-anterior hypothalamus (MPOA-AH) in monogamous and polygamous voles. Quantitative determinations were made of volume, cell number, and cell density for the anteroventral-periventriular nucleus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN-POA). Polygamous montane voles ( Microtus montanus) had a greater degree of sexual dimorphism in both cell groups than did monogamous prairie voles ( M. ochrogaster). Most notable was the complete absence of the AVPV in male montane voles; male montane voles also had a significantly larger SDN-POA volume than did females. The only sexual dimorphism in prairie voles was a greater cell density in the female AVPV. In addition, prairie voles had larger relative brain size than did montane voles. Comparative behavioral studies have revealed a correlation between the degree of sexual dimorphism in external morphology and mating system, i.e., polygamous species display greater levels of dimorphism than do monogamous species. The present results indicate that the effects of sexual selection can also be seen in those brain regions, like the hypothalamus, that underlie social and reproductive behavior. Moreover, these results support the hypothesis that neuroanatomic dimorphisms in the MPOA-AH may be related to sex differences in behavior.

Arginine-vasopressin immunoreactivity is not altered by photoperiod or gonadal hormones in the Syrian hamster ( Mesocricetus auratus)

The present study examined whether gonadal hormones or photoperiodic control influence arginine-vasopressin (AVP) immunoreactivity in the Syrian hamster ( Mesocricetus auratus) as has been reported in several other rodent species. Male hamsters were castrated or sham-castrated and exposed to LD 14/10 or LD 6/18 for 13 weeks. Photoperiod and castration significantly altered body weight and the levels of circulating testosterone. In sham-castrates, testis width was significantly reduced in hamsters housed in LD 6/18. In contrast, photoperiod and castration produced no detectable alterations in AVP immunoreactivity in various CNS sites including the bed nucleus of the stria terminales, the lateral septum and medial preoptic-anterior hypothalamus when measured by immunocytochemistry and radioimmunoassay of tissue punches. These data provide no evidence that AVP is regulated by either gonadal hormones or photoperiodic mechanisms in the Syrian hamster.

Testosterone alters the behavioral response of the medial preoptic-anterior hypothalamus to microinjection of arginine vasopressin in the hamster

The medial preoptic-anterior hypothalamus (MPOA-AH) is necessary for expression of several testosterone-dependent behaviors including a form of hamster scent marking, called flank marking. Since arginine vasopressin (AVP) plays a critical role in the control of flank marking by the MPOA-AH the present study examined whether testosterone can influence the amount of flank marking produced by AVP microinjected into the MPOA-AH. The dose-dependent induction of flank marking by AVP was found to be reduced by approximately 50% in castrated male hamsters when compared to intact or testosterone-treated castrates. These data demonstrate that testosterone influences the amount of flank marking produced by AVP within the MPOA-AH.

Medial preoptic-anterior hypothalamic lesions in prepubertal male cats: Effects on juvenile and adult sociosexual behaviors

Bilateral lesions of the medial preoptic-anterior hypothalamic (MP-AH) area were made in prepubertal male cats at 6–8 weeks of age. All subjects were subsequently reared in groups containing male and female peers, until the last phase of the juvenile period when an adult estrous female was inserted in these social groups. In spite of such optimal conditions for the practice of sociosexual behaviors during development, no sparing of adult male copulatory behavior was observed in these MP-AH animals during testing in adulthood. This finding, while consistent with earlier work on dogs, contrasts with the results obtained in prepubertally lesioned rats. Urine spraying, another sexually dimorphic behavior which is eliminated by MP-AH lesions in adult cats, was spared by prepubertal lesion placement. Heterotypical sexual behavior was not enhanced by prepubertal MP-AH lesion placement, as it is with postpubertal placement. In the present study, therefore, different behavioral systems influenced by the MP-AH area showed varying degrees of plasticity. As found in dogs, prepubertal MP-AH lesions enhanced and accelerated testosterone secretion in cats.

Medial preoptic-anterior hypothalamic lesions and sociosexual behavior of male goats

With the aid of x-ray ventriculography, lesions were placed in the medial preoptic-anterior hypothalamic (MP-AH) area of 5 adult male pygmy goats. The lesions resulted in a marked decrement in ejaculatory responses, as they have in previous studies on rats, cats, dogs and rhesus monkeys. The results illustrate the apparent universal effects of MP-AH lesions on copulatory behavior in mammalian species. Male sex-typical non-courtship responses of flehmen, self-enurination and penis licking were not altered by the MP-AH lesions. Since the non-courtship responses are displayed most frequently when male goats are sexually aroused, the results point to a specific effect of the lesions in disturbing a male's copulating performance while sparing other expressions of sexual arousal.