Centrally administered orexin/hypocretin activates HPA axis in rats

Kuru, Makiko; Ueta, Yoichi; Serino, Ryota; Nakazato, Masamitsu; Yamamoto, Yukiyo; Shibuya, Izumi; Yamashita, Hiroshi

doi:10.1097/00001756-200006260-00034

Cited by 266 publications

(173 citation statements)

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“…Footshock-sensitive neurons in lateral hypothalamus have been described that project to the PVN (Li and Sawchenko, 1998). Furthermore, hypocretin-1 induces c-Fos expression in the PVN (Ida et al, 2000a) and dose dependently stimulates ACTH and corticosterone release (Hagan et al, 1999;Ida et al, 2000a;Jaszberenyi et al, 2000;Kuru et al, 2000;Samson et al, 2002). Pretreatment with ␣-helical CRF, a CRF antagonist, blocks the corticosterone elevation induced by hcrt (Ida et al, 2000b;Jaszberenyi et al, 2000;Samson et al, 2002).…”

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.

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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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.

418

316

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“…These include feeding behavior (1, 3, 4), behavioral activity (5), sleep/awake (6,7,8), energy balance (9) and neuroendocrinological response (10). In addition to these functions, we have shown that intracisternal but not intraperitoneal injection of orexin-A dosedespondently stimulated gastric acid secretion in conscious rats (11).…”

Section: Introductionmentioning

confidence: 94%

Requirement of Intact Disulfide Bonds in Orexin-A-Induced Stimulation of Gastric Acid Secretion That Is Mediated by OX1 Receptor Activation

Okumura

Takeuchi

Motomura

et al. 2001

Biochemical and Biophysical Research Communications

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Orexin-A is a neuropeptide consisting 33 amino acids with two intrachain disulfide bonds, namely Cys6-Cys12 and Cys7-Cys14, and is a potent stimulator of food consumption and gastric acid secretion. In contrast, orexin-B, a peptide containing 28 amino acids without disulfide bond, which has no stimulatory action of gastric acid. The objective of the present study was to characterize the receptor-mediated mechanism of orexin-A-induced stimulation of gastric acid secretion using orexin-A-

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“…For example, the feedingpromoting actions of HCRT may reflect a potentially broader role of HCRT in appetitive processes (Willie et al, 2001). Additionally, ICV HCRT-1 elicits a variety of stresslike physiological and behavioral responses, including activation of the hypothalamo-pituitary-adrenal axis (Jaszberenyi et al, 2000;Kuru et al, 2000), increased c-fos expression (España et al, 2003), locomotor activation, grooming, and the chewing of inedible material (Nakamura et al, 2000;España et al, 2001). Intra-VTA infusions of HCRT-1 also provoked certain stress-like behaviors, including grooming.…”

Section: Hcrt-da Interactions In Aversive and Appetitive Conditionsmentioning

confidence: 99%

Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

Vittoz

Berridge

2005

Neuropsychopharmacol

171

114

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Hypocretins (HCRTs) modulate a variety of behavioral and physiological processes, in part via interactions with multiple ascending modulatory systems. Further, HCRT efferents from the lateral hypothalamus innervate midbrain dopamine (DA) nuclei, and DA cell bodies express HCRT receptors. Combined, these observations suggest that HCRT may influence behavioral state and/or statedependent processes via modulation of DA neurotransmission. The current studies used in vivo microdialysis in the unanesthetized rat to first characterize the effect of intracerebroventricular infusion of HCRT-1 (0.07, 0.7 nmol) on extracellular levels of DA within the prefrontal cortex (PFC) and nucleus accumbens (Acc). Electroencephalographic/electromyographic measures of sleep-wake state were collected along with select behavioral measures (eg locomotor activity, grooming). HCRT-1 dose-dependently increased PFC dialysate DA levels, and these increases were closely correlated with increases in time spent awake. In contrast, Acc DA levels were unaffected. Additional studies examined whether HCRT-1 acts directly within the ventral tegmental area (VTA) to selectively increase PFC DA efflux and modulate behavioral state. Unilateral infusion of HCRT-1 (0.1, 1.0 nmol) within the VTA increased PFC, but not Acc, DA levels. Importantly, intra-VTA infusion of HCRT-1 increased the time spent awake and grooming. Moreover, HCRT-induced increases in both time spent awake and time spent grooming were significantly correlated with post-infusion PFC DA levels. The current observations predict a prominent modulatory influence of HCRT on PFC-dependent cognitive and affective processes that results, in part, from actions within the VTA. Additionally, these observations suggest that the activation of VTA DA neurons contributes to the behavioral state-modulatory actions of HCRT.

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Centrally administered orexin/hypocretin activates HPA axis in rats

Cited by 266 publications

References 1 publication

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

Requirement of Intact Disulfide Bonds in Orexin-A-Induced Stimulation of Gastric Acid Secretion That Is Mediated by OX1 Receptor Activation

Hypocretin/Orexin Selectively Increases Dopamine Efflux within the Prefrontal Cortex: Involvement of the Ventral Tegmental Area

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