Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX 1 ) receptors, with downstream 5-HT 2C receptor involvement

Duxon, Mark S.; Stretton, Jennifer L.; Starr, Kathryn R.; Jones, Declan N.C.; Holland, Vicky; Riley, Graham J.; Jerman, Jeffrey C.; Brough, Stephen; Smart, Darren; Johns, Amanda; Chan, Wai N.; Porter, Rod A.; Upton, Neil

doi:10.1007/s002130000550

Cited by 87 publications

(41 citation statements)

References 22 publications

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“…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). Interestingly, hypocretin-deficient mice display diminished behavioral response to emotional stress, suggesting that hypocretinproducing neurons play a role in one of the efferent pathways of defense response (Kayaba et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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.

412

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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Section: Discussionmentioning

confidence: 99%

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.

412

316

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“…For instance, DIO and DR rats differ in monoaminergic function (13,25,26), sensitivity to glucose (32), leptin (28,30), and/or insulin (5). However, since orexin A-induced effects are sensitive to metabolic status (3,34) and the circadian cycle (10,53), and are mediated downstream by monoamines (2,9,11,16,39), these differences could also be explained by variation in orexin signaling between DIO and DR rats. Dopaminergic neurons in the substantia nigra that innervate the striatum are a critical component of locomotor activity, and dopamine receptor antagonists block orexin A-induced locomotor activity when administered in the ventral tegmental area (39).…”

Section: Discussionmentioning

confidence: 99%

Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats

Teske¹,

Levine²,

Kuskowski³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

139

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lectively-bred obesity-resistant [diet resistant (DR)] rats weigh less than obesity-prone [diet-induced obese (DIO)] rats, despite comparable daily caloric intake, suggesting phenotypic energy expenditure differences. Human data suggest that obesity is maintained by reduced ambulatory or spontaneous physical activity (SPA). The neuropeptide orexin A robustly stimulates SPA. We hypothesized that DR rats have greater: 1) basal SPA, 2) orexin A-induced SPA, and 3) preproorexin, orexin 1 and 2 receptor (OX1R and OX2R) mRNA, compared with DIO rats. A group of age-matched out-bred Sprague-Dawley rats were used as additional controls for the behavioral studies. DIO, DR, and Sprague-Dawley rats with dorsal-rostral lateral hypothalamic (rLHa) cannulas were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 l). SPA and food intake were measured for 2 h after injection. Preproorexin, OX1R and OX2R mRNA in the rLHa, and whole hypothalamus were measured by real-time RT-PCR. Orexin A significantly stimulated feeding in all rats. Orexin A-induced SPA was significantly greater in DR and Sprague-Dawley rats than in DIO rats. Two-mo-old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-moold DR rats had elevated OX1R and OX2R mRNA compared with DIO rats, although this increase was significant for OX2R only at this age. Thus DR rats show elevated basal and orexin A-induced SPA associated with increased OX1R and OX2R gene expression, suggesting that differences in orexin A signaling through OX1R and OX2R may mediate DIO and DR phenotypes.hypocretin; lateral hypothalamus; locomotor activity; diet-induced obesity.OUT-BRED MALE SPRAGUE-DAWLEY rats fed a high-energy diet display divergent body weight gain patterns. Approximately half of the rats become obese [diet induced obese (DIO)] while the other half remain lean [diet resistant (DR)]. DIO and DR rats can be prospectively identified before exposure to a highenergy diet based on sympathetic activation (32) and monoaminergic function (13,24,26), suggesting that differences in the propensity toward weight gain are due to differences in CNS function. To better understand the mechanism underlying the propensity or resistance to weight gain observed in the out-bred DIO and DR rats, Sprague-Dawley rats fed a high-fat diet were selectively bred for their weight gain. This selective breeding scheme produced two substrains of Sprague-Dawley rats that displayed divergent body weight gain patterns despite comparable caloric intake following chow feeding (29, 47), suggesting that differences in energy expenditure primarily underlie phenotypic differences in body weight gain patterns. It has been demonstrated that lean individuals spent more time standing and ambulating than obese individuals, and this amount of time remained fixed independent of body weight despite overfeeding lean or underfeeding mildly obese individuals (33). Similarly, differences in spontaneous physical activity (SPA) between lean and obese out-...

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“…Similarly, to determine whether the enhanced W and motor performance seen with WT mice in the wheel test can be prevented by an antagonism of Ox neurotransmission, we performed, in both WT and Ox Ϫ/Ϫ mice and just before the test during the lights period, an intraperitoneal injection of SB-334867, a brain penetrating Ox-1 receptor antagonist (Duxon et al, 2001;Smart et al, 2001;Soffin et al, 2002). The antagonist at a dose of 30 mg/kg had no effects at all on W, locomotion and sleep stages in the KO mice, whereas, in contrast, the same injection did significantly decrease W and locomotion and increase SWS in WT littermates and, as a result, the amount of W, SWS or locomotion was brought close to that seen with KO mice during the wheel test alone.…”

Section: Wheel Test Coupled With Drug Administrationmentioning

confidence: 99%

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.

195

170

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Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX 1 ) receptors, with downstream 5-HT 2C receptor involvement

Abstract: This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised.

Cited by 87 publications

References 22 publications

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

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

Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats

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

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