Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity

Jones, Declan N.C.; Gartlon, Jane; Parker, Frederick B.; Taylor, Simon; Routledge, Carol; Hemmati, Panida; Munton, Richard P.; Ashmeade, Tracey; Hatcher, Jon P.; Johns, Amanda; Porter, Rod A.; Hagan, Jim J.; Hunter, A. Jackie; Upton, Neil

doi:10.1007/s002130000551

Cited by 96 publications

(48 citation statements)

References 29 publications

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“…Here we extended these findings by showing a dose-related reduction in plasma prolactin following NmU (0.3-3 μg). Similar reductions in plasma prolactin levels are seen following i.c.v.-administered orexin-A (Hagan et al 1999;Jones et al 2001) and suggest that these neuropeptides may be involved in the inhibitory control of prolactin. One candidate for this role is DA, which when released from DA neurons in the tuberoinfundibular pathway potently inhibits prolactin release from the pituitary (Ben-Jonathon et al 1989).…”

Section: Discussionmentioning

confidence: 56%

“…administration of neuropeptides. For example, striatal and hypothalamic 5-HT metabolism are altered by orexin-B (Jones et al 2001). NmU significantly elevated 5-HT levels in the frontal cortex and hypothalamus, with both increased levels of 5-HT and decreased levels of its metabolites in the hypothalamus and hippocampus, suggesting decreased 5-HT utilisation.…”

Section: Discussionmentioning

confidence: 97%

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Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats

et al. 2004

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Rationale: Neuromedin-U (NmU) is an agonist at NMU1R and NMU2R. The brain distribution of NmU and its receptors, in particular NMU2R, suggests widespread central roles for NmU. In agreement, centrally administered NmU affects feeding behaviour, energy expenditure and pituitary output. Further central nervous system (CNS) roles for NmU warrant investigation. Objectives: To investigate the CNS role of NmU by mapping NMU1R and NMU2R mRNA and measuring the behavioural, endocrine, neurochemical and c-fos response to intracerebroventricular (i.c.v.) NmU. Methods: Binding affinity and functional potency of rat NmU was determined at human NMU1R and NMU2R. Expression of NMU1R and NMU2R mRNA in rat and human tissue was determined using semi-quantitative reverse-transcription polymerase chain reaction. In in-vivo studies, NmU was administered i.c.v. to male Sprague-Dawley rats, and changes in grooming, motor activity and pre-pulse inhibition (PPI) were assessed. In further studies, plasma endocrine hormones, v.).Results: NmU bound to NMU1R (K I , 0.11±0.02 nM) and NMU2R (K I , 0.21±0.05 nM) with equal affinity and was equally active at NMU1R (EC 50 , 1.25±0.05 nM) and NMU2R (EC 50 , 1.10±0.20 nM) in a functional assay. NMU2R mRNA expression was found at the highest levels in the CNS regions of both rat and human tissues. NMU1R mRNA expression was restricted to the periphery of both species with the exception of the rat amygdala. NmU caused a marked increase in grooming and motor activity but did not affect PPI. Further, NmU decreased plasma prolactin but did not affect levels of corticosterone, luteinising hormone or thyroid stimulating hormone. NmU elevated levels of 5-HT in the frontal cortex and hypothalamus, with decreased levels of its metabolites in the hippocampus and hypothalamus, but did not affect dopamine function. NmU markedly increased FLI in the nucleus accumbens, frontal cortex and central amygdala.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 97%

Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats

et al. 2004

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“…Indeed, the behaviors observed after hypocretin injection are similar to those observed during stress (Ida et al, 2000a), although they are less anxiogenic that the ones observed after CRF administration (Hagan et al, 1999). The hypocretins induce an intense grooming response accompanying the increase in arousal and locomotor activity (Hagan et al, 1999;Samson et al, 1999;Nakamura et al, 2000;Jones et al, 2001). These behavioral effects of hypocretins are blocked by an hcrt-r1 antagonist (Duxon et al, 2001).…”

Section: Discussionmentioning

confidence: 76%

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

Winsky‐Sommerer¹,

Yamanaka²,

Diano³

et al. 2004

J. Neurosci.

418

316

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The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.

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“…Finally, central application of orexins elicits active arousal and hyperactivity in rats, an effect prevented by SB-334867 (Hagan et al, 1999;Jones et al, 2001). Together, these results suggest that Ox neurons promote locomotion and behavioral arousal and thus contribute to the maintenance of W by enhancing locomotion.…”

mentioning

confidence: 72%

Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models

Anaclet¹,

Parmentier²,

Ouk³

et al. 2009

J. Neurosci.

198

170

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Effects of centrally administered orexin-B and orexin-A: a role for orexin-1 receptors in orexin-B-induced hyperactivity

Abstract: The present study has demonstrated a number of behavioural, neuroendocrine and neurochemical effects of orexin-B that distinguish it from orexin-A. Further, we have demonstrated a role for OX1 receptors in the actions of orexin-B upon motor activity.

Cited by 96 publications

References 29 publications

Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats

Localisation of NMU1R and NMU2R in human and rat central nervous system and effects of neuromedin-U following central administration in rats

Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response

Orexin/Hypocretin and Histamine: Distinct Roles in the Control of Wakefulness Demonstrated Using Knock-Out Mouse Models

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