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Microinjection of prostaglandin E2 and muscimol into the preoptic area in conscious rats: comparison of effects on plasma adrenocorticotrophic hormone (ACTH), body temperature, locomotor activity, and cardiovascular function.

The preoptic area (POA) is thought to play an important role in thermoregulation and fever. Local application of prostaglandin E2 (PGE2) to this region elicits increases in core body temperature, heart rate, and plasma levels of adrenocorticotrophic hormone (ACTH). Similar effects on body temperature and heart rate have also been reported after local application of the GABAA receptor agonist muscimol to the preoptic area. The purpose of this study was to assess and compare the effects of microinjection of PGE2 and muscimol into the preoptic area in the same chronically instrumented conscious rats on plasma levels of ACTH. Injection of either PGE2 (150 pmol/100 nL) or muscimol (20 or 80 pmol/100 nL) into the same sites in the preoptic area evoked increases in body temperature, heart rate, blood pressure, and plasma levels of ACTH, while significant increases in locomotor activity were apparent only after muscimol. These data confirm and extend previous findings and support the notion that neurons in the region of the preoptic area exert tonic inhibition on downstream mechanisms capable of increasing the activity of the hypothalamic-pituitary-adrenal (HPA) axis as well as sympathetic thermogenic and cardiac activity.

Adrenocorticotropic Hormone↗

Sex differences in dendritic structure in the preoptic area of the juvenile macaque monkey brain.

Quantitative analysis of Golgi-stained neurons in the preoptic area of the brain of prepuberal Macaca fascicularis monkeys indicated structural differences between males and females. Neurons of males had more dendritic bifurcations and a higher frequency of spines. The bifurcation difference appeared in all cell types and was concentrated in the ventrolateral preoptic area. The spine difference was greatest in the central region of the preoptic area. No differences in gross measurements of this brain region were found. These results suggest that sexual dimorphism in the function of the monkey preoptic area may be based on differences in neuronal structure.

Animals↗

Experience facilitates vomeronasal and olfactory influence on Fos expression in medial preoptic area during pheromone exposure or mating in male hamsters.

Chemosensory stimuli are essential for mating in male hamsters but either main olfactory or vomeronasal input is sufficient in sexually experienced males. Activation in central chemosensory pathways and medial preoptic area, after stimulation with female chemosignals or after mating, was estimated by counting neurons expressing Fos protein in experienced and naive males, with or without vomeronasal organ lesions. Regions counted included main and accessory olfactory bulbs, corticomedial amygdala, bed nucleus stria terminalis and medial preoptic area. Chemosensory stimulation was more effective in activating medial preoptic area in experienced than in naive males. In experienced males with vomeronasal organs removed, main olfactory input was as effective in activating medial preoptic area as was the combination of main and accessory input available to intact animals. As previously reported, the main olfactory input remaining after vomeronasal lesions in naive males was poorly effective in activating medial preoptic area, and these animals had impaired mating behavior. The change in access of chemosensory input to medial preoptic area after experience suggests that an experience-dependent synaptic modulation in this pathway, perhaps in the amygdala, may underlie some changes in mating behavior with experience.

Amygdala↗

Involvement of opioid peptides of the preoptic area during electroacupuncture analgesia.

The present work was to study the roles of opioid peptides in the preoptic area on electroacupuncture analgesia (EA), and the effects of opioid peptides on noradrenaline (NA) release in the preoptic area during EA. It was found that the pain threshold and the level of [Leu5] enkephalin (L-EK) or beta-endorphin (beta-EP) release in the perfusate were increased during EA, but the NA release from the preoptic area was decreased. Naloxone (15 microM) perfusion significantly reversed the increased pain threshold and the decreased NA release induced by acupuncture. The reversal of pain threshold and the decreased NA release induced by acupuncture. The reversal of pain threshold and NA release by naloxone was dose-dependent. Multimicropipettes and microiontophoresis were also used to study the effect of acupuncture. The inhibition of nociceptive neuronal discharges produced by electroacupuncture was closely related to the etorphine-sensitive neurons, and reversed by microiontophoretic application of naloxone. The results suggest that the inhibitory effect induced by electroacupuncture may be mediated by opioid peptides in the preoptic area.

Acupuncture Analgesia↗

Relationship between the thymus and neurochemical changes in the hypothalamus-preoptic area and prefrontal cortex in female rats with delayed puberty.

In female rats, aged 55-58 days with delayed puberty due to deficient growth and environmental stress, 5-hydroxyindoleacetic acid levels and serotonin turnover rate in the hypothalamus-preoptic area as well as body weight, body weight gain and relative weight of ovaries, uterus, adrenals and preputial glands were lower while serotonin and 5-hydroxyindoleacetic acid levels in the prefrontal cortex were higher when compared to normal rats with the latest onset of puberty aged 42-52 days. In rats with delayed puberty, multiple regression analysis revealed a significant negative dependence on dopamine turnover in the hypothalamus-preoptic area for body weight gain and, of all organs, for the relative weight of the thymus. A similar negative significant dependence on serotonin turnover rate in the prefrontal cortex was also found for the relative weight of thymus and spleen. The same analysis in the opposite direction revealed a significant negative dependence of 3,4-dihydroxyphenylacetic acid levels and dopamine turnover rate in the hypothalamus-preoptic area as well as serotonin turnover rate in the prefrontal cortex only on thymus weight. After separation of delayed pubertal rats into two groups, based on absolute ovarian weight, the rats in the low ovarian weight range and no signs of puberty exhibited: lower body weight gain, lower body weight, and lower relative weight only of thymus, ovaries and preputial glands in parallel with an increased dopamine turnover rate in the hypothalamus-preoptic area and serotonin turnover rate in the prefrontal cortex compared to the delayed pubertal rats in the high ovarian weight range and early signs of puberty. The results suggest that in rats with delayed puberty: (1) serotonergic activation in the hypothalamus-preoptic area is lower compared to normal puberty rats; (2) dopaminergic activation in the hypothalamus-preoptic area negatively affects body weight gain, thymus weight and initiation of puberty and (3) thymus weight is negatively implicated in dopaminergic activation in the hypothalamus-preoptic area and serotonergic activation in the prefrontal cortex and positively related to ovarian weight and early signs of puberty.

Animals↗

Direct neural connection from the medial preoptic area to the hypothalamic arcuate nucleus of the rat.

Direct neural connections from the medial preoptic area (MPOA) to the arcuate nucleus were studied on light and electron microscope level by a multistep experimental procedure. The hypothalamic deafferentation technique of Halász and Pupp (1965) was used in itself or was combined with electrolytic lesions. In order to eliminate all fibers of more rostral source traversing the medial preoptic area an extended rostral preoptic deafferentation was made, and a survival time of at least 3 weeks was chosen to allow for the complete disappearance of the degenerated fragments from the arcuate nucleus. In the main experimental group the medial preoptic area was destroyed by an electrolytic lesion 3 or more weeks following such rostral preoptic deafferentations. In these animals degenerated fibers and terminals certainly of preoptic origin were found distributed bilaterally, with a predominance on the side of the lesion. - These data suggest that axons originating from medial preoptic neurons terminate in the arcuate nucleus, thus constituting a preoptico-tuberal pathway.

Animals↗

Studies on the role of the preoptic area in the control of reproductive function in the rat.

The present study was designed to determine the effects of bilateral lesions restricted to the medial preoptic area on reproductive function in rats. Adult female rats were placed in a stereotaxic instrument, and bilateral lesions were made in the medial preoptic area of the diencephalon using an anodic current and platinum or stainless steel electrodes. Both types of lesions produced identical effects. Most animals with lesions restricted to the medial preoptic area showed repeated periods of pseudopregnancy for the duration of their lives. Ova were detected in the oviducts on the day of estrus between pseudopregnancies, and deciduomata could be produced by uterine traumatization during pseudopregnancy. Daily administration of lergotrile mesylate, a dopamine agonist, for about two weeks, to the pseudopregnant rats with lesions resulted in the appearance of normal 4 or 5-day estrous cycles. These results suggest that the medial preoptic area may not be necessary for ovulation in the rat, and that the normal function of the preoptic area in the control of reproductive cyclicity may be mediated via dopaminergic neurons. In agreement with earlier studies, we found that lesions that extended into the anterior hypothalamus resulted in constant estrus.

Acetonitriles↗

Role of the anterior hypothalamus-preoptic area in the regulation of courtship behavior in the male Canadian red-sided garter snake (Thamnophis sirtalis parietalis): lesion experiments.

Lesions of the medial preoptic area and/or the ventromedial hypothalamus resulted in an abrupt and immediate decline in courtship behavior in adult male Canadian red-sided garter snakes (Thamnophis sirtalis parietalis). Lesions of the more anterior portions of the preoptic area resulted in a more gradual, delayed decline in courtship behavior. Male snakes sustaining lesions dorsal, ventral, or caudal to the anterior hypothalamus-preoptic area exhibited no change in courtship behavior relative to controls. Measurements of testis size, spermatogenic stage, and circulation levels of androgens revealed no differences between any of the groups. There were marked differences in the change in hematocrit over time between the groups. These results indicate that the anterior hypothalamus-preoptic area is involved in the control of courtship behavior in the adult male red-sided garter snake. Moreover, it is suggested that the stimulus affecting the anterior hypothalamus-preoptic area to activate courtship is temperature related.

Androgens↗

Antisense mRNA for NPY-Y1 receptor in the medial preoptic area increases prolactin secretion.

We investigated the participation of neuropeptide Y-Y1 receptors within the medial preoptic area in luteinizing hormone, follicle-stimulating hormone and prolactin release. Four bilateral microinjections of sense (control) or antisense 18-base oligonucleotides of messenger ribonucleic acid (mRNA) (250 ng) corresponding to the NH2-terminus of the neuropeptide Y1 receptor were performed at 12-h intervals for two days into the medial preoptic area of ovariectomized Wistar rats (N = 16), weighing 180 to 200 g, treated with estrogen (50 microg) and progesterone (25 mg) two days before the experiments between 8.00 and 10:00 a.m. Blockade of Y1 receptor synthesis in the medial preoptic area by the antisense mRNA did not change plasma luteinizing hormone or follicle-stimulating hormone but did increase prolactin from 19.6 +/- 5.9 ng/ml in the sense group to 52.9 +/- 9.6 ng/ml in the antisense group. The plasma hormones were measured by radioimmunoassay and the values are reported as mean +/- SEM. These data suggest that endogenous neuropeptide Y in the medial preoptic area has an inhibitory action on prolactin secretion through Y1 receptors.

Animals↗

Characterization of tritiated noradrenaline release from the rat preoptic area with microdialysis in vivo.

Present techniques are unable to provide a sensitive and accurate index of noradrenergic activity in the rat preoptic area. In this study, we have examined the brainstem A1 noradrenergic input to the preoptic area using a new technique whereby [3H]noradrenaline is preloaded into the preoptic area and release of radioactivity from this region is measured subsequently using microdialysis in vivo. Electrical stimulation of the ipsilateral A1 area for 20 min at 5, 10, and 15 Hz evoked significant increases in dialysate radioactivity that were repeatable and frequency-dependent. After removal of calcium from the perfusion medium, basal release of radioactivity was markedly reduced and the effect of A1 stimulation abolished. Changing to a 100 mM K+ medium evoked an increase in the release of radioactivity that was sixfold greater than that seen after A1 stimulation. Separation of the dialysate with HPLC showed that 33% of the increase in measured radioactivity after A1 stimulation was directly attributable to [3H]noradrenaline and the remainder to the metabolites vanillylmandelic acid, 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylglycol. In contrast, the increase in radioactivity after K+ depolarization was due almost completely to [3H]noradrenaline. Addition of 10 microM clonidine to the perfusion medium markedly reduced basal release of radioactivity, but had no effect on evoked release following A1 stimulation. Conversely, perfusion with 10 microM yohimbine had no effect on basal release, but significantly increased evoked release after A1 stimulation. These results now provide a characterization of noradrenergic activity in the preoptic area and indicate the importance of the A1 noradrenergic input to this region. The technique of measuring radioactivity with microdialysis after preloading with [3H]noradrenaline provides a relatively simple, sensitive index of noradrenergic activity in vivo with good temporal resolution.

Animals↗

The role of alpha-2 receptors in the medial preoptic area in the regulation of sleep-wakefulness and body temperature.

The study was conducted on 48 free-moving male rats to find out the role of the medial preoptic alpha2 receptors in the regulation of sleep and body temperature. Recording electrodes for assessment of sleep-wakefulness, and injector cannulae for injection of drugs in the medial preoptic area were chronically fixed on the skulls of the animals. The noradrenergic fibres projecting to the medial preoptic area were destroyed in 24 rats by administration of 6-hydroxydopamine at the ventral noradrenergic bundle. Though arousal was produced in normal rats by the injection of the alpha2 adrenergic agonist, clonidine, at the medial preoptic area, it induced sedation in rats with noradrenergic fibre lesion. Clonidine did not alter the rectal temperature in normal rats but it induced hypothermia in lesioned rats. Injection of alpha2 antagonist, yohimbine, at the medial preoptic area induced sleep in rats with intact noradrenergic fibres. However, the sleep inducing effect of this drug was very much attenuated in the lesioned animals. There was no significant change in body temperature, in both these groups of animals, after yohimbine administration. The study indicates the role of presynaptic alpha2 adrenergic receptors in arousal response and indirectly supports the contention that the alpha1 postsynaptic receptors at the medial preoptic area are involved in hypnogenesis. It also suggests that the thermal changes induced by adrenergic system are mediated through alpha1 postsynaptic receptors. But the thermal changes do not contribute towards the induced alterations in sleep-wakefulness. It is proposed that there should be separate sets of noradrenergic terminals for regulation of sleep and body temperature.

Administration, Topical↗

[The role of the medial preoptic area in the organization of paradoxical sleep].

Influence of electrical stimulation of the medial preoptic area of cats on characteristics of paradoxical sleep and activity of medial preoptic neurons were studied in the course of sleep-waking cycle. Low-frequency stimulation of this structure in the state of slow-wave sleep evoked short-latency electrocortical desynchronization and induced transition to paradoxical sleep or paradocical sleep-like state. The same stimulation during the whole period of paradoxical sleep results in a reduction of its duration, practically complete disappearance of tonic stage, and increase in the density of rapid eye movements in phasic stage. The vast majority of meurons in the medial preoptic area decreased their firing rates during quiet waking and slow-wave sleep and dramatically increased their activity during paradoxical sleep. More than 50% of such neurons displayed activation 20-70 s prior to the appearance of electrocorticographic correlates of paradoxical sleep. Some neurons were selectively active during paradoxical sleep. Approximately 50% of cells increased their firing rates a few seconds prior to and/or during series of rapid eye movements. The results suggest that the medial preoptic area contains the units of the executive system (network) of paradoxical sleep and are involved in the mechanisms of neocortical desynchronization.

Animals↗

Long-term effects of preoptic area knife cuts on the maternal behavior of postpartum rats.

Knife cuts severing the lateral connections of the medial preoptic area disrupt maternal behavior in postpartum rats. In these studies the knife cuts were produced 1-2 days prior to behavioral testing. The present study examined whether preoptic area knife cuts produce long-term deficits in maternal behavior. Nulliparous Charles River CD rats received knife cuts severing the lateral connections of the medial preoptic area or sham cuts. Approximately 2 weeks later they were mated. All females delivered young 22-23 days after mating, and litter size did not differ between the groups. Females with preoptic knife cuts cleaned their young, built nests (albeit of inferior quality), crouched over their young in a nursing posture, and lactated. The major deficit shown was the near total elimination of retrieval behavior. Females with preoptic knife cuts, however, were capable of performing the oral-motor responses associated with hoarding behavior. These results show that severing the lateral connections of the medial preoptic area does produce long-term deficits in maternal behavior, particularly with respect to maternal retrieving.

Animals↗

[Effects of noradrenaline and dopamine in preoptic area on acupuncture analgesia].

Previous work has shown that activation of catecholamine in the preoptic area is to the disadvantage of acupuncture analgesia. In this work microinjection and push-pull perfusion as well as HPLC-ECD were used to observe the effect of noradrenaline and dopamine in this area on acupuncture analgesia. The results indicated that microinjection of noradrenaline (0.5 microgram/unilateral) into the preoptic area could attenuate acupuncture analgesia, while dopamine (2 micrograms/unilateral) had no effect on acupuncture analgesia. During acupuncture analgesia, the contents of noradrenaline and MHPG in the perfusate from the preoptic area were markedly decreased, and that of dopamine, however, was not changed significantly. The above results suggest that activating noradrenaline, but not dopamine, exerts antagonistic effect on acupuncture analgesia.

Acupuncture Analgesia↗

Correlation between the sexually dimorphic aromatase of the preoptic area and sexual behavior in quail: effects of neonatal manipulations of the hormonal milieu.

The aromatase of the preoptic area is significantly more active in males than in females. This sex dimorphism in enzyme activity is still found in birds that have been gonadectomized and treated with a same dose of testosterone. This suggests that the sex difference is not the result of a differential activation by the adult hormonal environment but rather is organized neonatally by steroid hormones. As the central aromatization of testosterone is a limiting step in the activation of copulatory behavior by testosterone, the lower aromatase activity in the preoptic area of females might be responsible, at least in part, for their lower sensitivity to the activating effects of testosterone on behavior. Three experiments were carried out to determine whether early manipulations of the hormonal environment, which are known to differentiate sexual behavior, also affect in a permanent way the aromatase activity in the preoptic area. Injection of estradiol benzoate into male embryos on day 9 of incubation decreased the preoptic aromatase activity in parallel to its demasculinizing effect on behavior. Unexpectedly the same treatment tended to increase enzyme activity in females so that the physiological relevance of the observed enzymatic change remains questionable. In two independent experiments, we confirmed that neonatal ovariectomy of female quail interferes with their behavioral differentiation. Females gonadectomized at 4 days post-hatch showed significantly more male-type sexual behavior as adult in response to testosterone than females gonadectomized at the age of 5 weeks. These experiments also confirmed that the preoptic aromatase activity is higher in males than in females but no evidence for an effect of the age of gonadectomy on the enzyme activity could be obtained. The sex difference and experimental modifications observed in the aromatase activity of the preoptic area were not seen in the posterior hypothalamus demonstrating that these effects are specific. The mechanisms controlling the sex difference in aromatase activity are discussed. The difference might be organized by the action of embryonic steroids as suggested by the changes observed in males injected with estradiol benzoate in egg. Alternatively, activational mechanisms cannot be ruled out at present. In one experiment, the activity of the preoptic aromatase was positively correlated with the sexual activity of the birds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Presence of sex difference of cytochrome P-450 in the rat preoptic area and hypothalamus with reference to coexistence with oxytocin.

Localization of female type cytochrome P-450 (F1) in the preoptic area and hypothalamus of the rat was examined immunocytochemically using antiserum against purified hepatic P-450 (F1). This antiserum recognizes both P-450 (F1) and P-450 (M3). Western immunoblotting using the antiserum demonstrated that female rat brain contains P-450 (F1) but not P-450 (M3), since microsomes from the brain and liver displayed only one immunoreactive band at 50 kD, coinciding with that of P-450 (F1) purified from female rat liver. On the other hand, the male brain has P-450 (M3) but not P-450 (F1), as liver- and brain-derived microsomes produced single band at 49 kD, which represents a mol. wt. identical to that of P-450 (M3) extracted from male rat liver. These results indicate that P-450 (F1)-like immunoreactivity (LI) occurs in the female rat brain, while P-450 (M3)-LI takes place in the male rat brain. Immunocytochemical analysis further demonstrated the detailed cellular localization of these two P-450-LIs in the preoptic area and hypothalamus of female and male rats. Localization of P-450 (F1)-LI in the female rat hypothalamus resembled that of P-450 (M3)-LI in the male rat hypothalamus. Magnocellular neurosecretory neurons in the paraventricular nucleus and supraoptic nucleus were labeled and were found to contain oxytocin but lack vasopressin when serial sections of these areas were analyzed. In addition, groups of immunoreactive cells were seen in the median preoptic nucleus, medial and lateral preoptic area, caudal portion of the bed nucleus of the stria terminalis, lateral hypothalamus at the level of the paraventricular nucleus, periventricular zone from the preoptic area to the paraventricular nucleus, and parvocellular portion of the paraventricular nucleus.

Animals↗

Antagonism of central pressor response to angiotensin II by alpha-human atrial natriuretic polypeptide at the preoptic area and posterior hypothalamus in rats.

Effects of alpha-human atrial natriuretic polypeptides (alpha-hANP) on pressor responses to angiotensin II (AII) were assessed at the preoptic area, posterior hypothalamus and central amygdaloid nucleus (ACE) in spontaneously hypertensive (SHR) and control normotensive Wistar-Kyoto (WKY) rats. Angiotensin II, administered intracerebroventricularly, at a dose of 100 ng produced a marked pressor response in hypertensive, as well as in normotensive rats and the response was potentiated in hypertensive rats. The response was antagonized in a dose-dependent manner by administration of alpha-hANP into the preoptic area and posterior hypothalamus but not to the amygdaloid nucleus. The antagonism was more marked in hypertensive than in normotensive rats. Angiotensin II, when injected directly to the preoptic area at a small dose of 10 ng similarly evoked a marked pressor response, which was augmented in hypertensive rats. This response was also antagonized by coadministration of alpha-hANP to the preoptic area in hypertensive but not in normotensive rats. The results suggest that the antagonistic relationship between ANP and AII exists at the preoptic area and posterior hypothalamus, probably implying that the activity of the ANP and AII systems in brain play a role in centrally controlling the cardiovascular system and is altered at these areas in genetically hypertensive rats.

Amygdala↗

Preoptic area estradiol-concentrating neurons project to the hypothalamus in female rats.

Estradiol (E2)-concentrating neurons afferent to the ventromedial nucleus of the hypothalamus (VMH) were identified by combining fluorescent retrograde tracing with steroid hormone autoradiography. The majority of E2-concentrating neurons that projected to the VMH were located in the medial preoptic area. In the entire medial preoptic area, 10.0% of the E2-sensitive neurons sent axons that terminated in the VMH. Twenty percent of the E2-concentrating neurons located in the periventricular preoptic area projected to the VMH. Of the E2-concentrating neurons found in the medial preoptic nucleus, 8.0% sent axons directly to the VMH. The bed nucleus of the stria terminalis, septum, and medial amygdala contained very few E2-receptive neurons that projected to the VMH. Preoptic area E2-concentrating neurons that project to the VMH may be part of a neural circuit that influences reproduction.

Animals↗