Showing papers on "Orexin-A published in 2012"
TL;DR: The role of ORX, specifically orexin-A (ORX-A) in the bed nucleus of the stria terminalis (BNST) on anxiety-like behaviors in rats was determined to be dependent on NMDA-type glutamate receptor activity, as pre-injecting the NMDA antagonist AP5 into the BNST blocked anxiogenic effects of local ORX-a injections.
98 citations
TL;DR: Exogenous nesfatin‐1 acts on other appetite regulatory peptides in a time‐ and feeding status‐dependent, as well as tissue‐specific, manner in goldfish, and interactions with ghrelin, CCK and orexin are indicated.
Abstract: Nesfatin-1 is a novel anorectic peptide encoded in the precursor protein nucleobindin-2 (NUCB2). We recently reported the presence and appetite suppressing effects of nesfatin-1 in goldfish. Nesfatin-1 has been co-localised with ghrelin in the stomach of rats. Whether nesfatin-1 influences other appetite regulatory peptides in goldfish remains unclear. The main objectives of the present study were to investigate whether nesfatin-1 co-localises ghrelin in goldfish, and to test whether exogenous nesfatin-1 influences endogenous ghrelin, cholecystokinin (CCK) and orexin A (OXA). We found co-localisation of nesfatin-1-like and ghrelin-like immunoreactivity in the enteroendocrine cells of the goldfish anterior intestine (J-loop). Furthermore, co-localisation of ghrelin and nesfatin-1 was also observed in the posterior nucleus lateralis tuberis of the goldfish hypothalamus, a brain region implicated in the regulation of food intake. These findings suggest a functional relationship between ghrelin and nesfatin-1 in goldfish. In support of this, i.c.v. administration of goldfish (gf) nesfatin-1 [25 ng/g body weight (BW)], suppressed food intake and the expression of mRNAs encoding preproghrelin, ghrelin receptor (GHS-R 1a-1), CCK and NUCB2 in the forebrain of fed fish, as well as ghrelin and NUCB2 mRNA in the hypothalamus of unfed fish, both at 1 h post-injection. Nesfatin-1 stimulated hypothalamic CCK mRNA expression at 30 min post-injection in fed fish, and inhibited OXA mRNA in the unfed fish hypothalamus 1 h post-injection. Similarly, i.c.v. injections of gfghrelin (1 ng/g BW), although stimulating food intake, suppressed NUCB2 and preproghrelin mRNAs, but not ghrelin receptor mRNA expression in the forebrain. It is also evident that exogenous ghrelin and nesfatin-1 mRNAs encoding these peptides. Our novel results indicate interactions between nesfatin-1 and ghrelin, CCK and orexin, and show that nesfatin-1 acts on other appetite regulatory peptides in a time- and feeding status-dependent, as well as tissue-specific, manner in goldfish.
91 citations
TL;DR: Almorexant specifically inhibits the actions of orexin A and dissociates very slowly from OX(2)R as measured functionally and in radioligand binding, and is sufficient to promote sleep in mice.
Abstract: Study Objectives: Orexin peptides activate orexin 1 and orexin 2 receptors (OX1R and OX2R), regulate locomotion and sleep-wake. The dual OX1R/OX2R antagonist almorexant reduces activity and promotes sleep in multiple species, including man. The relative contributions of the two receptors in locomotion and sleep/wake regulation were investigated in mice. Design: Mice lacking orexin receptors were used to determine the contribution of OX1R and OX2R to orexin A-induced locomotion and to almorex- ant-induced sleep. Setting: N/A. Patients or Participants: C57BL/6J mice and OX1R +/+ , OX1R -/- , OX2R +/+ , OX2R -/- and OX1R -/- /OX2R -/- mice. Interventions: Intracerebroventricular orexin A; oral dosing of almorexant. Measurements and Results: Almorexant attenuated orexin A-induced locomotion. As in other species, almorexant dose-dependently increased rapid eye movement sleep (REM) and nonREM sleep in mice. Almorexant and orexin A were ineffective in OX1R -/- /OX2R -/- mice. Both orexin A- induced locomotion and sleep induction by almorexant were absent in OX2R -/- mice. Interestingly, almorexant did not induce cataplexy in wild-type mice under conditions where cataplexy was seen in mice lacking orexins and in OX1R -/- /OX2R -/- mice. Almorexant dissociates very slowly from OX2R as measured functionally and in radioligand binding. Under non equilibrium conditions in vitro, almorexant was a dual antagonist whereas at equilibrium, almorexant became OX2R selective. Conclusions: In vivo, almorexant specifically inhibits the actions of orexin A. The two known orexin receptors mediate sleep induction by almorex- ant and orexin A-induced locomotion. However, OX2R activation mediates locomotion induction by orexin A and antagonism of OX2R is sufficient to promote sleep in mice.
84 citations
TL;DR: The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes, and Orexin A‐immunoreactive neurones in the lateral hypothalamus project to the RVLM.
Abstract: BACKGROUND AND PURPOSE The rostral ventrolateral medulla (RVLM) maintains sympathetic nerve activity (SNA), and integrates adaptive reflexes. Orexin A-immunoreactive neurones in the lateral hypothalamus project to the RVLM. Microinjection of orexin A into RVLM increases blood pressure and heart rate. However, the expression of orexin receptors, and effects of orexin A in the RVLM on splanchnic SNA (sSNA), respiration and adaptive reflexes are unknown.
EXPERIMENTAL APPROACH The effect of orexin A on baseline cardio-respiratory variables as well as the somato-sympathetic, baroreceptor and chemoreceptor reflexes in RVLM were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats (n= 50). orexin A and its receptors were detected with fluorescence immunohistochemistry.
KEY RESULTS Tyrosine hydroxylase-immunoreactive neurones in the RVLM were frequently co-localized with orexin 1 (OX1) and orexin 2 (OX2) receptors and closely apposed to orexin A-immunoreactive terminals. Orexin A injected into the RVLM was pressor and sympatho-excitatory. Peak effects were observed at 50 pmol with increased mean arterial pressure (42 mmHg) and SNA (45%). Responses to orexin A (50 pmol) were attenuated by the OX1 receptor antagonist, SB334867, and reproduced by the OX2 receptor agonist, [Ala11, D-Leu15]orexin B. Orexin A attenuated the somato-sympathetic reflex but increased baroreflex sensitivity. Orexin A increased or reduced sympatho-excitation following hypoxia or hypercapnia respectively.
CONCLUSIONS AND IMPLICATIONS Although central cardio-respiratory control mechanisms at rest do not rely on orexin, responses to adaptive stimuli are dramatically affected by the functional state of orexin receptors.
83 citations
TL;DR: Results suggest that subdivisions and subnuclei of the extended amygdala are specific targets of the orexinergic system and the entopeduncular nucleus has been newly identified as another target for orexInergic fibers with a high density.
Abstract: The orexinergic system interacts with several functional states of emotions, stress, hunger, wakefulness and behavioral arousal through four pathways originating in the lateral hypothalamus (LH). Hundreds of orexinergic efferents have been described by tracing studies and direct immunohistochemistry of orexin in the forebrain, olfactory regions, hippocampus, amygdala, septum, basal ganglia, thalamus, hypothalamus, brain stem and spinal cord. Most of these tracing studies investigated the whole orexinergic projection to all regions of the intracranial part of the CNS. To identify the orexinergic efferents at the subnuclear level of resolution, we focussed on the orexinergic target in the amygdala, which is substantially involved in the LH output and contributes mostly to the functional outcome of the orexinergic system and the basal ganglia. Immunohistochemical identification of axonal orexin A and orexin B in male adult rats has been performed on serial sections. In the extended amygdala many new orexinergic targets were found in the anterior amygdaloid area (dense), anterior cortical nucleus (moderate), amygdalostriatal transition region (moderate), basolateral regions (moderate), basomedial nucleus (moderate), several bed nucleus of the stria terminals regions (few to dense), central amygdaloid subdivisions (dense), posteromedial cortical nucleus (moderate) and medial amygdaloid subnuclei (dense). Furthermore, the entopeduncular nucleus has been newly identified as another target for orexinergic fibers with a high density. These results suggest that subdivisions and subnuclei of the extended amygdala are specific targets of the orexinergic system.
71 citations
TL;DR: The neuroprotective effects of OxA are evaluated in a novel immortalized primary embryonic rat hypothalamic cell line and it is demonstrated for the first time that OxA increases cell viability during hydrogen peroxide challenge, decreases hydrogenperoxide-induced lipid peroxidative stress, and decreases caspase 3/7 induced apoptosis in an in vitro hypothalamic model.
56 citations
TL;DR: It is estimated that the energetic cost of SPA after orexin A RLH injection accounts for approximately 61% of the extra caloric intake associated with HF intake, suggesting additional effects of orexins.
Abstract: There is significant variability in diet-induced obesity (DIO) among humans and rodents, which has been associated with differences in intrinsic spontaneous physical activity (SPA). The orexin neuropeptides positively modulate SPA through multiple brain sites, but the effects of DIO on orexin's activity are not well understood. In this study, we tested the hypothesis that DIO sensitivity is mediated by decreased SPA and changes in the function of the orexins. As a DIO model, we used male Sprague-Dawley rats fed a high-fat (HF; 45% kcal from fat) or a low-fat (LF; 10% kcal from fat) diet for 10 wk. We measured SPA before and after HF or LF feeding and expression of orexin receptors by real-time PCR after dietary treatments. We tested DIO effects on orexin signaling by measuring SPA after injection of orexin A in the rostral lateral hypothalamus (RLH) before and after 10 wk of HF feeding. Finally, we tested whether daily orexin A RLH injections prevent DIO caused by HF feeding. Our results show that resistance to DIO is associated with an increase in SPA, SPA after injection of orexin A in RLH, and orexin receptor expression in sites that mediate orexin's effect on SPA, including RLH. We show that daily injections of orexin peptide in RLH prevent DIO without altering food intake. We estimate that the energetic cost of SPA after orexin A RLH injection accounts for approximately 61% of the extra caloric intake associated with HF intake, suggesting additional effects of orexins. In summary, our results suggest that variability in DIO sensitivity is mediated through adaptations in the activity of the orexin peptides and their receptors.
52 citations
TL;DR: Results highlight a critical role of OXA signalling, via OX1R, in activation of brain stress system to morphine withdrawal and suggest that all orexinergic subpopulations in the lateral hypothalamic area contribute in this response.
Abstract: Both the hypothalamus-pituitary-adrenal (HPA) axis and the extrahypothalamic brain stress system are key elements of the neural circuitry that regulates the negative states during abstinence from chronic drug exposure. Orexins have recently been hypothesized to modulate the extended amygdala and to contribute to the negative emotional state associated with dependence. This study examined the impact of chronic morphine and withdrawal on the lateral hypothalamic (LH) orexin A (OXA) gene expression and activity as well as OXA involvement in the brain stress response to morphine abstinence. Male Wistar rats received chronic morphine followed by naloxone to precipitate withdrawal. The selective OX1R antagonist SB334867 was used to examine whether orexins' activity is related to somatic symptoms of opiate withdrawal and alterations in HPA axis and extended amygdala in rats dependent on morphine. OXA mRNA was induced in the hypothalamus during morphine withdrawal, which was accompanied by activation of OXA neurons in the LH. Importantly, SB334867 attenuated the somatic symptoms of withdrawal, and reduced morphine withdrawal-induced c-Fos expression in the nucleus accumbens (NAc) shell, bed nucleus of stria terminalis, central amygdala and hypothalamic paraventricular nucleus, but did not modify the HPA axis activity. These results highlight a critical role of OXA signalling, via OX1R, in activation of brain stress system to morphine withdrawal and suggest that all orexinergic subpopulations in the lateral hypothalamic area contribute in this response.
51 citations
TL;DR: Findings that orexins might have anti-depressive roles are supported by the effects of orexin 2 receptor (OX2R) activation on cell signaling in CHO cells over-expressing OX2R and in mouse hypothalamus cell line CLU172, and several isoforms of PKC may be involved in prolonged CREB phosphorylation.
46 citations
TL;DR: Findings indicate that Alterations in orexin regulation of septohippocampal cholinergic activity may contribute to age‐related dysfunctions in arousal, learning, and memory.
Abstract: The medial septum (MS) of the basal forebrain contains cholinergic neurons that project to the hippocampus, support cognitive function, and are implicated in age-related cognitive decline Hypothalamic orexin/hypocretin neurons innervate and modulate basal forebrain cholinergic neurons and provide direct inputs to the hippocampus However, the precise role of orexin in modulating hippocampal cholinergic transmission—and how these interactions are altered in aging—is unknown Here, orexin A was administered to CA1 and the MS of young (3–4 months) and aged (27–29 months) Fisher 344/Brown Norway rats, and hippocampal acetylcholine efflux was analyzed by in vivo microdialysis At both infusion sites, orexin A dose-dependently increased hippocampal acetylcholine in young, but not aged rats Moreover, immunohistochemical characterization of the MS revealed no change in cholinergic cell bodies in aged animals, but a significant decrease in orexin fiber innervation to cholinergic cells These findings indicate that: (1) Orexin A modulates hippocampal cholinergic neurotransmission directly and transsynaptically in young animals, (2) Aged animals are unresponsive to orexin A, and (3) Aged animals undergo an intrinsic reduction in orexin innervation to cholinergic cells within the MS Alterations in orexin regulation of septohippocampal cholinergic activity may contribute to age-related dysfunctions in arousal, learning, and memory Synapse, 2012 © 2011 Wiley Periodicals, Inc
45 citations
TL;DR: The findings indicate that activity of orexinergic neurons is inhibited by propofol anesthesia, and the orexIn signals in basal forebrain are involved in anesthesia–arousal regulation from propofl anesthesia.
Abstract: Background Hypothalamic orexinergic neurons play a critical role in the promotion and maintenance of wakefulness in mammals. Previous studies have demonstrated that activities of orexinergic neurons were inhibited by isoflurane and sevoflurane, and microinjection of orexin facilitated the emergence from volatile anesthesia. In this study we first examined the hypothesis that the activity of orexin neurons is inhibited by propofol anesthesia. Moreover, the role of the orexinergic signals in basal forebrain in regulating the anesthesia-arousal cycle of propofol anesthesia is also elucidated. Methods Rats were killed at 0, 30, 60, and 120 minutes of propofol infusion as well as at the time the righting reflex returned after the termination of anesthesia. Activated orexinergic neurons were detected by c-Fos expression. The plasma concentrations of orexin-A were measured by radioimmunoassay. Orexin-A (30 or 100 pmol) or the orexin-1 receptor antagonist, SB-334867A (5 or 20 μg), was microinjected into the basal forebrain 15 minutes before propofol infusion, or 15 minutes before the termination of propofol infusion. The loss and the return of the righting reflex time were recorded as the induction and the emergence time. Results Propofol anesthesia resulted in an inhibition of orexinergic neuron activity as demonstrated by the reduced numbers of c-Fos-immunoreactive orexinergic neurons. The activities of orexinergic neurons were restored when rats emerged from anesthesia. Propofol anesthesia decreased plasma orexin-A concentrations. Intrabasalis microinjection of orexin-A had no effect on the induction time but facilitated the emergence from propofol anesthesia. Inversely, intrabasalis microinjection of the orexin-1 receptor antagonist SB-334867A delayed the emergence from propofol anesthesia. Conclusions Our findings indicate that activity of orexinergic neurons is inhibited by propofol anesthesia, and the orexin signals in basal forebrain are involved in anesthesia-arousal regulation from propofol anesthesia.
TL;DR: The data demonstrated that the ORXA-induced antinociception in formalin test is mainly mediated through the OX1R in LPGi which might play a potential role in processing the pain information associated with descending pain modulation.
TL;DR: The results showed that unilateral intra-VTA administration of orexin A during conditioning phase induced CPP in a dose-dependent manner, and the role of intra-accumbal dopamine receptors in development (acquisition) of reward-related behaviors in the rats was examined.
TL;DR: Spike pattern analysis revealed orexin increases interevent interval by reducing the number of single spikes and bursts, which suggests orexIn may reduce overall firing rate by suppressing spike initiation and burst maintenance in GnRH neurons.
Abstract: GnRH neurons are critical for the central regulation of fertility, integrating steroidal, metabolic and other cues GnRH neurons appear to lack receptors for many of these cues, suggesting involvement of afferent systems to convey information Orexin A (orexin) is of interest in this regard as a neuromodulator that up-regulates metabolic activity, increases wakefulness, and affects GnRH/LH release We examined the electrophysiological response of GnRH neurons to orexin application and how this response changes with estradiol and time of day in a defined animal model Mice were either ovariectomized (OVX) or OVX and implanted with estradiol capsules (OVX+E) GnRH neurons from OVX+E mice exhibit low firing rates in the morning, due to estradiol-negative feedback, and high firing rates in the evening, due to positive feedback Orexin inhibited activity of GnRH neurons from OVX mice independent of time of day In GnRH neurons from OVX+E mice, orexin was inhibitory during the evening, suggesting orexin inhibition is not altered by estradiol No effect of orexin was observed in OVX+E morning recordings, due to low basal GnRH activity Inhibitory effects of orexin were mediated by the type 1 orexin receptor, but antagonism of this receptor did not increase GnRH neuron activity during estradiol-negative feedback Spike pattern analysis revealed orexin increases interevent interval by reducing the number of single spikes and bursts Orexin reduced spikes/burst and burst duration but did not affect intraburst interval This suggests orexin may reduce overall firing rate by suppressing spike initiation and burst maintenance in GnRH neurons
TL;DR: The developmental expression of orex in A supports the hypothesis that orexin expression only appears post-natally, and appears to be a good candidate to play a pivotal role in connecting olfactory and hypothalamic pathways.
Abstract: It is well known that olfaction influences food intake, and conversely, that an individual's nutritional status modulates olfactory sensitivity. However, what is still poorly understood is the neuronal correlate of this relationship, as well as the connections between the olfactory bulb and the hypothalamus. The goal of this report is to analyze the relationship between the olfactory bulb and hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide that is thought to play a role in states of sleep/wakefulness. Interestingly, orexin A has also been described as a food intake stimulator. Such an effect may be due in part to the stimulation of the olfactory bulbar pathway. In rats, orexin positive cells are concentrated strictly in the lateral hypothalamus, while their projections invade nearly the entire brain including the olfactory system. Therefore, orexin appears to be a good candidate to play a pivotal role in connecting olfactory and hypothalamic pathways. So far, orexin has been described in rats, however, there is still a lack of information concerning its expression in the brains of adult and developing mice. In this context, we revisited the orexin A pattern in adult and developing mice using immunohistological methods and confocal microscopy. Besides minor differences, orexin A immunostaining in mice shares many features with those observed in rats. In the olfactory bulb, even though there are few orexin projections, they reach all the different layers of the olfactory bulb. In contrast to the presence of orexin projections in the main olfactory bulb, almost none have been found in the accessory olfactory bulb. The developmental expression of orexin A supports the hypothesis that orexin expression only appears post-natally.
TL;DR: The direct excitatory action of orexin-A on layer 2/3 mPFC neurons may contribute to the modulation of PFC activity, and play a role in cognitive arousal.
TL;DR: Comparable potency of orexin A, orex in B and [Ala(11)-D-Leu(15)]orexin B suggests a predominant role of OX(2)R in the studied phenomenon, which provides new insights into the role of oxins in CNS as potential neuroprotective factors.
01 Jan 2012
TL;DR: It is shown that the OXR1-null mice phenocopies the differentiation defect observed in the ligand- null mice indicating that OXr1 relays OX’s differentiation and thermogenic function, which constitutes an important thermoregulatory mechanism that defends against cold and obesity.
Abstract: Orexin A (OX) is a small excitatory neuropeptide hormone that stimulates feeding, wakefulness and energy expenditure via a pair of G-coupled protein receptors, namely orexin receptor-1 (OXR1) and orexin receptor-2 (OXR2). OX-deficient mice are sensitive to obesity despite being hypophagic. The obesogenic effect of OX-deletion is due to brown adipose tissue (BAT) dysfunction, a defect that originates during fetal growth. Brown preadipocytes in OX-null mice display undifferentiated histological appearance and fail to support both diet- and cold-induced thermogenesis. We show that the OXR1-null mice phenocopies the differentiation defect observed in the ligand-null mice indicating that OXR1 relays OX’s differentiation and thermogenic function. Consistent with this, OX fails to induce differentiation in cultured OXR1-null preadipocytes. Thus, OX signaling via OXR1 constitutes an important thermoregulatory mechanism that defends against cold and obesity.
TL;DR: The results of the present study indicate the involvement of OXA in EA analgesia via OX1R in an opioid-independent way.
Abstract: Orexin A (OXA, hypocretin/hcrt 1) is a newly discovered potential analgesic substance. However, whether OXA is involved in acupuncture analgesia remains unknown. The present study was designed to investigate the involvement of spinal OXA in electroacupuncture (EA) analgesia. A modified rat model of post-laparotomy pain was adopted and evaluated. Von Frey filaments were used to measure mechanical allodynia of the hind paw and abdomen. EA at 2/15 Hz or 2/100 Hz was performed once on the bilateral ST36 and SP6 for 30 min perioperatively. SB-334867, a selective orexin 1 receptor (OX1R) antagonist with a higher affinity for OXA than OXB, was intrathecally injected to observe its effect on EA analgesia. OXA at 0.3 nmol and EA at 2/15 Hz produced respective analgesic effects on the model (P 0.05). In addition, naloxone, a selective opioid receptor antagonist, failed to antagonize OXA-induced analgesia (P>0.05). The results of the present study indicate the involvement of OXA in EA analgesia via OX1R in an opioid-independent way.
TL;DR: The results suggest that orexin A and B are produced in the porcine uterus and that their release is dependent on the hormonal status of animals.
TL;DR: It is suggested that in cultured rat cortical neurons orexins, acting at OX2 receptors coupled to PTX-sensitive Gi protein, inhibit cyclic AMP synthesis.
Abstract: Orexins A and B are newly discovered neuropeptides with pleiotropic activity. They signal through two G protein-coupled receptors: OX1 and OX2. In this study, we examined the expression of orexin receptors and effects of the receptors’ activation on cyclic AMP formation in the primary neuronal cell cultures from rat cerebral cortex. Both types of orexin receptors were expressed in rat cortical neurons; the level of OX2R was markedly higher compared to OX1R. Orexin A (an agonist of OX1R and OX2R) and [Ala11-D-Leu15]orexin B (a selective agonist of OX2R) did not affect basal cyclic AMP formation in the primary neuronal cell cultures. Both peptides (0.001–1 μM) inhibited, in a concentration-dependent manner and IC50 values in low nanomolar range, the increase in the nucleotide production evoked by forskolin (1 μM; a direct activator of adenylyl cyclase), pituitary adenylate cyclase-activating polypeptide (PACAP27; 0.1 μM), and vasoactive intestinal peptide (VIP; 3 μM). Effects of orexin A on forskolin-, PACAP27-, and VIP-stimulated cyclic AMP synthesis were blocked by TCS OX2 29 (a selective antagonist of OX2R), and unaffected by SB 408124 (a selective antagonist of OX1R). Pretreatment of neuronal cell cultures with pertussis toxin (PTX) abolished the inhibitory action of orexin A on forskolin- and PACAP-stimulated cyclic AMP accumulation. It is suggested that in cultured rat cortical neurons orexins, acting at OX2 receptors coupled to PTX-sensitive Gi protein, inhibit cyclic AMP synthesis.
TL;DR: Out of the five putative biomarkers measured, blood concentration of S100B and orexin A may be helpful in differentiating parasomnic pediatric patients with and without epilepsy.
TL;DR: Findings indicates that orexins enhances the hyperexcitable and hypersyncronic cortical epileptic activity induced by focal application of penicillin-G.
TL;DR: In this article, the effects of orexins on survival of rat C6 glioma cells, an experimental model for studies on glioblastoma multiforme (GBM), were reported.
Abstract: Orexin A and orexin B (also known as hypocretins) are closely related peptides synthesized by hypothalamic neurons. They orchestrate diverse central and peripheral processes by stimulation of two G-protein coupled receptors, OX1R and OX2R. Recent studies have demonstrated the ability of orexins to promote a robust apoptosis in different cancer cells in culture and a potent growth reduction of human colon tumors in mice xenografts. Here we report effects of orexins on survival of rat C6 glioma cells, an experimental model for studies on glioblastoma multiforme (GBM). Quantitative real-time PCR demonstrated the expression of both types of orexin receptors in C6 cells. Orexin A and orexin B did not affect rat C6 glioma cell proliferation as assessed by [3H]thymidine incorporation assay. Incubation of the cells with orexin A (0.001–1 μM) resulted in a marked decrease of cell viability. The observed effect was caspase-dependent, as it was blocked by Z-VAD-fmk, a pan caspase inhibitor. In addition to that, a parallel increase in caspase-3 activity was observed. It is suggested that stimulation of orexin receptors induces death of rat C6 glioma cells through activation of caspase pathway.
TL;DR: The results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR1) antagonists, but is blocked by OxR antagonists and absent in brain slices from orexin knockout mice.
TL;DR: Intramolecular FRET sensor forms of these receptors were functional and able to report the kinetics of agonist-mediated activation, and response of the OX1 and OX2 sensors to orexin A was slow, consistent with a multistep binding and activation process.
TL;DR: Orexin might be a possible target in THC as well as nicotine dependence, taking into account the effect of THC on energy homeostasis in the circuit of reward and motivation and its impact on appetite and body weight.
Abstract: Background: The orexins (hypocretins) are neuropeptides with an origin in the lateral hypothalamus. They have been found to be crucial within the context of drug
TL;DR: The findings indicate that orexin A and B cause epileptic activity.
TL;DR: The data suggest that orexins exert arousal effects on alcohol-induced unconscious rats by the promotion of cortical activity through activation of histaminergic, noradrenergic and serotonergic systems.
TL;DR: The results suggest that endogenous orexin-A in the brain is involved in the vagal-dependent stimulation of gastric contractions in non-fasted rats.
Abstract: Background
Increasing evidence has indicated that brain orexin plays a vital role in the regulation of gastrointestinal (GI) physiology such as gastric acid secretion and GI motility. The aim of this study was to elucidate the effects and mechanisms of orexin on gastric motility in non-fasted rats.