Neuropeptide FF and neuropeptide VF inhibit GABAergic neurotransmission in parvocellular neurons of the rat hypothalamic paraventricular nucleus

Neuropeptide FF (NPFF) and neuropeptide VF (NPVF) are octapeptides belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain, including central autonomic and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1 and NPFF2 receptors that are abundantly expressed in the rat brain, including the hypothalamic paraventricular nucleus (PVN), an autonomic nucleus critical for the secretion of neurohormones and the regulation of sympathetic outflow. In this study, we examined, using whole cell patch-clamp recordings in the brain slice, the effects of NPFF and NPVF on inhibitory GABAergic synaptic input to parvocellular PVN neurons. Under voltage-clamp conditions, NPFF and NPVF reversibly and in a concentration-dependent manner reduced the evoked bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) in parvocellular PVN neurons by 25 and 31%, respectively. RF9, a potent and selective NPFF receptor antagonist, blocked NPFF-induced reduction of IPSCs. Recordings of miniature IPSCs in these neurons following NPFF and NPVF applications showed a reduction in frequency but not amplitude, indicating a presynaptic locus of action for these peptides. Under current-clamp conditions, NPVF and NPFF caused depolarization (6-9 mV) of neurons that persisted in the presence of TTX but was abolished in the presence of bicuculline. Collectively, these data provide evidence for a disinhibitory role of NPFF and NPVF in the hypothalamic PVN via an attenuation of GABAergic inhibitory input to parvocellular neurons of this nucleus and explain the central autonomic effects of NPFF.     

Galanin-like immunoreactivity in the chicken brain

The anatomical distribution of neurons containing galanin has been studied in the central nervous system of the chicken by means of immunocytochemistry using antisera against rat galanin. Major populations of immunostained perikarya were detected in several brain areas. The majority of galanin-immunoreactive cell bodies was present in the hypothalamus and in the caudal brainstem. Extensive groups of labeled perikarya were found in the paraventricular, periventricular, dorsomedial and tuberal hypothalamic nuclei, and in the nucleus of the solitary tract in the medulla oblongata. In the telencephalon, immunoreactive perikarya were observed in the preoptic area, in the lateral septal nucleus and in the hippocampus. The mesencephalon contained only a few galanin-positive perikarya located in the interpeduncular nucleus. Immunoreactive nerve fibers of varying density were detected in all subdivisions of the brain. Dense accumulations of galanin-positive fibers were seen in the preoptic area, periventricular region of the diencephalon, the ventral hypothalamus, the median eminence, the central gray of the brainstem, and the dorsomedial caudal medulla. The distributional pattern of galanin-immunoreactive neurons suggests a possible involvement of a galanin-like peptide in several neuroregulatory mechanisms.     

Plasma hormone levels and central c-Fos expression in ferrets after systemic administration of cholecystokinin

Posterior pituitary hormone secretion and central neural expression of the immediate-early gene product c-Fos was examined in adult ferrets after intravenous administration of CCK octapeptide. Pharmacological doses of CCK (1, 5, 10, or 50 microg/kg) did not induce emesis, but elicited behavioral signs of nausea and dose-related increases in plasma vasopressin (AVP) levels without significant increases in plasma oxytocin (OT) levels. CCK activated neuronal c-Fos expression in several brain stem viscerosensory regions, including a dose-related activation of neurons in the dorsal vagal complex (DVC). Activated brain stem neurons included catecholaminergic and glucagon-like peptide-1-positive cells in the DVC and ventrolateral medulla. In the forebrain, activated neurons were prevalent in the paraventricular and supraoptic nuclei of the hypothalamus and also were observed in the central nucleus of the amygdala and bed nucleus of the stria terminalis. Activated hypothalamic neurons included cells that were immunoreactive for AVP, OT, and corticotropin-releasing factor. Comparable patterns of brain stem and forebrain c-Fos activation were observed in ferrets after intraperitoneal injection of lithium chloride (LiCl; 86 mg/kg), a classic emetic agent. However, LiCl activated more neurons in the area postrema and fewer neurons in the nucleus of the solitary tract compared with CCK. Together with results from previous studies in rodents, our findings support the view that nauseogenic treatments activate similar central neural circuits in emetic and nonemetic species, despite differences in treatment-induced emesis and pituitary hormone secretion.     

Identification of growth-hormone- and prolactin-containing neurons within the avian brain

Prolactin (PRL)- and growth-hormone (GH)-containing perikarya and fibers independent of the anterior pituitary gland have been reported to exist in the central nervous system of several mammalian species. The specific distributions of PRL- or GH-like neurons in the avian forebrain and midbrain, however, have not been reported. The objective of the study was to identify GH- and PRL-containing neurons in the hypothalamus and a few extrahypothalamic areas of two avian species. Brain and peripheral blood samples were collected from laying and broody turkey hens and ring doves. Broody turkey hens and doves had significantly higher plasma PRL concentrations compared with laying hens. Coronal brain sections were prepared and immunostained using anti-turkey GH and anti-chicken synthetic PRL antibodies. In turkey hens, the most dense GH-immunoreactive (ir) perikarya and fibers were found in hippocampus (Hp), periventricular hypothalamic nucleus, paraventricular nucleus, inferior hypothalamic nucleus, infundibular hypothalamic nucleus, medial and lateral septal area, and external zone of the median eminence (ME). In the ring dove, a similar pattern of distribution of GH-ir neurons was noticed at the brain sites listed above except that GH-ir fibers and granules were found only in the internal zone of ME and not in the external zone. In both turkeys and doves, the most immunoreactive PRL-ir perikarya and fibers were found in the medial and lateral septal area, Hp (turkey only), and bed nucleus of the stria terminalis pars magnocellularis. There were no apparent differences in the staining pattern of GH- or PRL-ir neurons between the laying and broody states in either species. However, the presence of GH-ir- and PRL-ir perikarya and fibers in several hypothalamic nuclei indicates that GH and PRL may influence parental behavior, food intake, autonomic nervous system function, and/or reproduction.     

Dopamine- and cyclic AMP-regulated phosphoprotein-immunoreactive neurons activated by acute stress are innervated by fiber terminals immunopositive for pituitary adenylate cyclase-activating polypeptide in the extended amygdala in the rat

The bed nuclei of the stria terminalis (BST) and the central nucleus of the amygdala are highly heterogeneous structures, which form one functional unit, the so-called extended amygdala. Several studies described increased c-fos expression following acute stress in this brain area, confirming its central role in the modulation/regulation of stress responses. The oval nucleus of the BST and the central amygdala exhibit a dense network of pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive (ir) fiber terminals. In addition, several dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32)-immunoreactive neurons were also observed here. Because the extended amygdala plays an important role in the central autonomic regulation during stress and the distribution of PACAP-ir and that of DARPP-32-ir nervous structures overlap, the aims of this study were to investigate the possible activation of DARPP-32-ir neurons following acute systemic stress and to demonstrate synaptic interactions between DARPP-32-ir neurons and fiber terminals immunopositive for PACAP.In summary, this study provided morphological evidence that acute stress resulted in the activation of DARPP-32 neurons, which were innervated by PACAP-ir neuronal structures in the extended amygdala. Furthermore, interaction between neuropeptides/neurotransmitters and phosphoproteins was also demonstrated.     

Calcitonin gene-related peptide: detailed immunohistochemical distribution in the central nervous system

With the use of an antiserum generated in rabbits against synthetic human calcitonin gene-related peptide (CGRP) the distribution of CGRP-like immunoreactive cell bodies and nerve fibers was studied in the rat central nervous system. A detailed stereotaxic atlas of CGRP-like neurons was prepared. CGRP-like immunoreactivity was widely distributed in the rat central nervous system. CGRP positive cell bodies were observed in the preoptic area and hypothalamus (medial preoptic, periventricular, anterior hypothalamic nuclei, perifornical area, medial forebrain bundle), premamillary nucleus, amygdala medialis, hippocampus and dentate gyrus, central gray and the ventromedial nucleus of the thalamus. In the midbrain a large cluster of cells was contained in the peripeduncular area ventral to the medial geniculate body. In the hindbrain cholinergic motor nuclei (III, IV, V, VI, VII XII) contained CGRP-immunoreactivity. Cell bodies were also observed in the ventral tegmental nucleus, the parabrachial nuclei, superior olive and nucleus ambiguus. The ventral horn cells of the spinal cord, the trigeminal and dorsal root ganglia also contained CGRP-immunoreactivity. Dense accumulations of fibers were observed in the amydala centralis, caudal portion of the caudate putamen, sensory trigeminal area, substantia gelatinosa, dorsal horn of the spinal cord (laminae I and II). Other areas containing CGRP-immunoreactive fibers are the septal area, nucleus of the stria terminalis, preoptic and hypothalamic nuclei (e.g., medial preoptic, periventricular, dorsomedial, median eminence), medial forebrain bundle, central gray, medial geniculate body, peripeduncular area, interpeduncular nucleus, cochlear nucleus, parabrachial nuclei, superior olive, nucleus tractus solitarii, and in the confines of clusters of cell bodies. Some fibers were also noted in the anterior and posterior pituitary and the sensory ganglia. As with other newly described brain neuropeptides it can only be conjectured that CGRP has a neuroregulatory action on a variety of functions throughout the brain and spinal cord.     

Autonomic and neuroendocrine actions of adrenomedullin in the brain: mechanisms for homeostasis

In addition to its role as a potent vasodilator, adrenomedullin (ADM) affects an animal's physiological status through its effects in the brain. We have shown that circulating ADM activates neurons, including nitric oxide (NO)-producing neurons, in autonomic centers of the brain such as the hypothalamic paraventricular nucleus (PVN). Systemic ADM gains access to the brain through the area postrema (AP), a brainstem circumventricular organ, and the PVN is a major target of these ADM-sensitive AP neurons. Neurons expressing the preproADM (ppADM) gene are distributed throughout the brain, with high levels in autonomic centers. Lipopolysaccharide (LPS, immune stress), restraint (psychological stress), and 24 h dehydration all down-regulate ppADM gene expression in different subsets of autonomic centers. Receptor-activity-modifying protein (RAMP) 2 and RAMP3, ADM receptor subunits, are expressed in autonomic centers including the PVN and supraoptic nucleus. Intracerebroventricular injections of ADM increase arterial pressure, heart rate, tyrosine hydroxylase mRNA levels in the locus coeruleus, plasma levels of ACTH, and NO production in the hypothalamus. ADM excites putative GABAergic and cholinergic neurons in dissociated cells from a basal forebrain integrative center, the diagonal band of Broca. These results demonstrate that the signalling components necessary for ADM to influence physiological systems are present in the brain and that ADM is an important transmitter of brain autonomic pathways which are involved in regulating homeostatic balance.     

Efferent ACTH-IR opiocortin projections from nucleus tractus solitarius: a hypothalamic deafferentation study

The distribution of opiocortin (OR-ir) immunoreactive fibers was examined immunocytochemically throughout the brain in rats following surgical isolation of the arcuate opiocortin-ir neuronal pool in the medial basal hypothalamus (MBH). Fibers which emanate from this pool were completely severed and thus eliminated from the rest of the brain, leaving intact those which can be identified immunocytochemically as opiocortin-ir projections from the medullary pool located in the nucleus tractus solitarius (NTS). These studies reveal a unique organizational pattern of proopiomelanocortin (POMC) peptidergic neuronal systems and demonstrate that several pontine and medullary regions receive projections from both the hypothalamic (arcuate) and medullary (NTS) opiocortin-ir perikarya. Comparative analyses of deafferented and control brains reveal that certain brainstem autonomic centers such as parabrachial (PB), locus coeruleus (LC), nucleus paragiganticellularis (PGi) are recipients of fibers which emanate from both arcuate and NTS opiocortin-ir perikarya. Areas which receive projections from arcuate opiocortin-ir neurons alone include forebrain and hypothalamic nuclei as well as the periaqueductal grey.     

Functional Organization of Brain Pathways Subserving the Baroreceptor Reflex: Studies in Conscious Animals Using Immediate Early Gene Expression

1. This paper reviews studies carried out in our laboratory in which we have used the c-fos functional mapping method, in combination with other methods, to determine the functional organization of central baroreceptor pathways as they operate in the conscious rabbit.2. First, we showed that periods of induced hypertension or hypotension each result in a specific and reproducible pattern of activation of neurons in the brainstem and forebrain. In particular, hypotension (but not hypertension) results in the activation of catecholamine neurons in the medulla and pons and vasopressin-synthesizing neurons in the hypothalamus.3. The activation of medullary cell groups in response to induced hypertension or hypotension in the conscious rabbit is almost entirely dependent on inputs from arterial baroreceptors, while the activation of hypothalamic vasopressin-synthesising neurons in response to hypotension is largely dependent on baroreceptors, although an increase in circulating angiotensin also appears to contribute.4. Discrete groups of neurons in the rostral ventrolateral medulla (RVLM) and A5 area in the pons are the major groups of spinally projecting neurons activated by baroreceptor unloading. In contrast, spinally projecting neurons in the paraventricular nucleus in the hypothalamus appear to be largely unaffected by baroreceptor signals.5. Direct afferent inputs to RVLM neurons in response to increases or decreases in arterial pressure originate primarily from other medullary nuclei, particularly neurons located in the caudal and intermediate levels of the ventrolateral medulla (CVLM and IVLM), as well as in the nucleus tractus solitarius (NTS).6. There is also a direct projection from barosensory neurons in the NTS to the CVLM/IVLM region, which is activated by baroreceptor inputs.7. Collectively, the results of our studies in conscious animals indicate that baroreceptor signals reach all levels of the brain. With regard to the baroreceptor reflex control of sympathetic activity, our studies are consistent with previous studies in anesthetized animals, but in addition reveal other previously unrecognized pathways that also contribute to this reflex regulation.     

Ontogeny of the FMRFamide-immunoreactivity in the rat forebrain and diencephalon

Ontogeny of the FMRFamide (molluscan cardioexcitatory neuropeptide)-containing structures in the forebrain and diencephalon of the rat was investigated by employing immunohistochemical methods. FMRFamide-like immunoreacted (FMRF-IR) fibers first appeared in the borders of the periventricular zone and the preoptic area at embryonic day 18 (E18). Toward birth, the FMRF-IR fibers gradually increased both in immunoreactivity and in number in these areas. A pronounced increase in FMRF-IR was also found in the septum, the arcuate nucleus, the median eminence, the paraventricular nucleus and the amygdaloid complex. A few FMRF-IR fibers appeared at the prenatal stage in the caudate nucleus, the bed nucleus of the stria terminalis, the dorsomedial nucleus and the cortex. The first FMRFamide-immunoreactive neurons were seen in the caudate-putamen and the amygdaloid complex at E21. These FMRF-IR cells increased in immunoreactivity and a significant number of cells was noted in these nuclei in the adult rat. The highest density of FMRF-IR neurons, especially in the amygdala and tuberal hypothalamic area, was detected at postnatal two weeks (P15). FMRFamide-like immunoreactivity in the forebrain and diencephalon appeared in the cell fibers prior to that observed in the cell bodies. This may suggest that some of the immunoreacted fibers may have originated from the lower areas of the rat brain. High densities of FMRF-IR cells present in the embryonic and early postnatal stages may indicate that FMRFamide is an important factor involved in developmental organization of the central nervous system. These results also indicate a differential genesis of FMRF-IR neuronal groups in different regions.     

Distribution of NT-IR perikarya in the brain of the guinea pig with special reference to cardiovascular centers in the medulla oblongata

The occurrence and distribution of neurotensin-immunoreactive (NT-IR) perikarya was studied in the central nervous system of the guinea pig using a newly raised antibody (KN 1). Numerous NT-IR perikarya were found in the nuclei amygdaloidei, nuclei septi interventriculare, hypothalamus, nucleus parafascicularis thalami, substantia grisea centralis mesencephali, ventral medulla oblongata, nucleus solitarius and spinal cord. The distribution of NT-IR perikarya was similar to that previously described in the rat and monkey. In the gyrus cinguli, hippocampus and nucleus olfactorius, though, no NT-IR neurons were detected in this investigation. Additional immunoreactive perikarya, however, were observed in areas of the ventral medulla oblongata, namely in the nucleus paragigantocellularis, nucleus retrofacialis and nucleus raphe obscurus. The relevance of the NT-IR perikarya within the ventral medulla oblongata is discussed with respect to other neuropeptides, which are found in this area, and to cardiovascular regulation.     

Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat.

The central nucleus of the amygdala, bed nucleus of the stria terminalis, and central gray are important components of the neural circuitry responsible for autonomic and behavioral responses to threatening or stressful stimuli. Neurons of the amygdala and bed nucleus of the stria terminalis that project to the midbrain central gray were tested for the presence of peptide immunoreactivity. To accomplish this aim, a combined immunohistochemical and retrograde tracing technique was used. Maximal retrograde labeling was observed in the amygdala and bed nucleus of the stria terminalis after injections of retrograde tracer into the caudal ventrolateral midbrain central gray. The majority of the retrogradely labeled neurons in the amygdala were located in the medial central nucleus, although many neurons were also observed in the lateral subdivision of the central nucleus. Most of the retrogradely labeled neurons in the BST were located in the ventral and posterior lateral subdivisions, although cells were also observed in most other subdivisions. Retrogradely labeled neurotensin, corticotropin releasing factor (CRF), and somatostatin neurons were mainly observed in the lateral central nucleus and the dorsal lateral BST. Retrogradely labeled substance P-immunoreactive cells were found in the medial central nucleus and the posterior and ventral lateral BST. Enkephalin-immunoreactive retrogradely labeled cells were not observed in the amygdala or bed nucleus of the stria terminalis. A few cells in the hypothalamus (paraventricular and lateral hypothalamic nuclei) that project to the central gray also contained CRF and neurotensin immunoreactivity. The results suggest the amygdala and the bed nucleus of the stria terminalis are a major forebrain source of CRF, neurotensin, somatostatin, and substance P terminals in the midbrain central gray.     

侧脑室注射肾上腺髓质素增加大鼠心血管相关核团中c-fos的表达并激活脑内一氧化氮神经元

本研究利用Fos蛋白和一氧化氮合酶(nNOS)双重免疫组化方法,观察侧腑脑室注射肾上腺髓质素(adrenomedullin,ADM)对大鼠心血管相关核中c-fos表达及一氧化氮神经元的影响,以探讨ADM在中枢的作用部位并研究其在中枢的作用是否有NO神经元参与。侧脑室注射ADM(1nmol／kg,3nmol／kg)诱发脑干的孤束核、最后区、蓝斑核、臂旁核和外侧巨细胞旁核,下丘脑的室旁核、视上核才腹内侧核以及前脑的中央杏仁核和外侧缰核等多个部位的心血管中枢出现大量Fos样免疫反应神经元。侧脑室注射ADM(3nmol／kg),引起脑干的孤束核、外侧巨细胞旁核,下丘脑的室旁核、视上核内的Fos-nNOS双标神经元增加;ADM(1nmol／kg)亦可引起室旁核、视上核内的Fos-nNOS双标神经元增加,而对孤束核、外侧巨细胞旁核内的Fos-nNOS双标神经元无影响。降钙素基因相关肽(calcitonin gene—related peptide,CGRP)受体拈抗剂CGRP8-37(30nmol／kg)可明显减弱此效应。以上结果表明,ADM可兴奋脑内多个心血管相关核闭的神经元并激活室旁核、视上核、孤束核及外侧巨细胞核内一氧化氮神经元,此效应可能部分山CGRP受体介导。     

Neuronal inputs from the hypothalamus and brain stem to the medial preoptic area of the ram: neurochemical correlates and comparison to the ewe

The retrograde tracer, FluoroGold, was used to trace the neuronal inputs from the septum, hypothalamus, and brain stem to the region of the GnRH neurons in the rostral preoptic area of the ram and to compare these imputs with those in the ewe. Sex differences were found in the number of retrogradely labeled cells in the dorsomedial and ventromedial nuclei. Retrogradely labeled cells were also observed in the lateral septum, preoptic area, organum vasculosum of the lamina terminalis, bed nucleus of the stria terminalis, stria terminalis, subfornical organ, periventricular nucleus, anterior hypothalamic area, lateral hypothalamus, arcuate nucleus, and posterior hypothalamus. These sex differences may partially explain sex differences in how GnRH secretion is regulated. Fluorescence immunohistochemistry was used to determine the neurochemical identity of some of these cells in the ram. Very few tyrosine hydroxylase-containing neurons in the A14 group (<1%), ACTH-containing neurons (<1%), and neuropeptide Y-containing neurons (1-5%) in the arcuate nucleus contained FluoroGold. The ventrolateral medulla and parabrachial nucleus contained the main populations of FluoroGold-containing neurons in the brain stem. Retrogradely labeled neurons were also observed in the nucleus of the solitary tract, dorsal raphe nucleus, and periaqueductal gray matter. Virtually all FluoroGold-containing cells in the ventrolateral medulla and about half of these cells in the nucleus of the solitary tract also stained for dopamine beta-hydroxylase. No other retrogradely labeled cells in the brain stem were noradrenergic. Although dopamine, beta-endorphin, and neuropeptide Y have been implicated in the regulation of GnRH secretion in males, it is unlikely that these neurotransmitters regulate GnRH secretion via direct inputs to GnRH neurons.     

Identification and characterization of novel mammalian neuropeptide FF-like peptides that attenuate morphine-induced antinociception

The two mammalian neuropeptides NPFF and NPAF have been shown to have important roles in nociception, anxiety, learning and memory, and cardiovascular reflex. Two receptors (FF1 and FF2) have been molecularly identified for NPFF and NPAF. We have now characterized a novel gene designated NPVF that encodes two neuropeptides highly similar to NPFF. NPVF mRNA was detected specifically in a region between the dorsomedial and ventromedial hypothalamic nuclei. NPVF-derived peptides displayed higher affinity for FF1 than NPFF-derived peptides, but showed poor agonist activity for FF2. Following intracerebral ventricular administration, a NPVF-derived peptide blocked morphine-induced analgesia more potently than NPFF in both acute and inflammatory models of pain. In situ hybridization analysis revealed distinct expression patterns of FF1 and FF2 in the rat central nervous system. FF1 was broadly distributed, with the highest levels found in specific regions of the limbic system and the brainstem where NPVF-producing neurons were shown to project. FF2, in contrast, was mostly expressed in the spinal cord and some regions of the thalamus. These results indicate that the endogenous ligands for FF1 and FF2 are NPVF- and NPFF-derived peptides, respectively, and suggest that the NPVF/FF1 system may be an important part of endogenous anti-opioid mechanism.     

Physiological and Neurochemical Aspects of Corticotropin-Releasing Factor Actions in the Brain: The Role of the Locus Coeruleus

Corticotropin-releasing factor (CRF) is both a major regulator of the hypothalamo-pituitary-adrenal (HPA) axis and the activity of the autonomic nervous system. Besides, it exerts numerous effects on other physiological functions such as appetite control, motor and cognitive behavior and immune function. The basis for these effects is constituted by its distribution in hypothalamic and extrahypothalamic brain areas, the latter being represented by limbic structures such as the central nucleus of the amygdala or by brain stem neurons such as the locus coeruleus (LC) or nucleus of the solitary tract (NTS). The effects of CRF are mediated through recently described CRF-receptor subtypes, whose molecular biology, biochemistry and pharmacological regulation are discussed in detail. In the second part of this review, we will focus on the physiology of CRF-systems in the brain, with a particular emphasis on cardiovascular regulation, respiration, appetite control and stress-related behavior. Finally, the role of the locus coeruleus in the control of CRF-mediated behavioral activities is discussed. The interaction of noradrenergic and CRF-neurons clearly implies that CRF appears to directly activate LC neurons in a stressful situation, thus ultimately coordinating the bodily response to a stressful stimulus.     

兔脑内Orexin B免疫阳性神经元的分布定位

采用免疫组织化学方法研究了10只青紫蓝兔脑内Orexin B免疫阳性神经元的分布定位。结果显示,Orexin B免疫阳性神经元分布于下丘脑的室旁核、背内侧核、穹隆周核、外侧区和后区以及底丘脑的未定带。以下丘脑背内侧核、穹隆周核和外侧区的阳性神经元数量较多,下丘脑室旁核、后区和未定带较少。表明了兔脑内Orexin B免疫阳性神经元的分布与Orexin A免疫阳性神经元的分布存在一些差异,提示两种Orexin的产生部位和生理功能可能也存在差异。     

Neuronal effects of orexins: relevant to sympathetic and cardiovascular functions

Orexin A and B, also called hypocretin 1 and 2, were recently discovered in the hypothalamus. This organ, in which a number of neuropeptides have been demonstrated to stimulate or suppress food intake, is considered important for the regulation of appetite and energy homeostasis. Orexins were initially reported as a regulator of food intake. More recent reports suggest their possible important roles in the multiple functions of neuronal systems, such as narcolepsy, a sleep disorder. Orexins and their receptors are distributed in neural tissue and brain regions involved in the autonomic and neuroendocrine control. Functional studies have shown that these peptides evoke changes in cardiovascular and sympathetic responses. The data from our in vivo and in vitro studies suggest that the peptide acting on neurons in the hypothalamic paraventricular nucleus increases the cardiovascular responses. This review will focus on the neural effects of orexins and how these peptides may participate in the regulation of cardiovascular and sympathetic functions.