Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action

España, Rodrigo A.; Baldo, Brian A.; Kelley, Ann E.; Berridge, Craig W.

doi:10.1016/s0306-4522(01)00319-0

Cited by 292 publications

(233 citation statements)

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“…Similar to previous observations (España et al, 2001), ICV-administered HCRT-1 dosedependently increased EEG/EMG measures of time spent awake (treatment F 2,13 ¼ 13.13, Po0.01; time F 9,117 ¼ 9.76, Po0.001; treatment Â time F 18,117 ¼ 4.16, Po0.001). Two animals were excluded from these analyses due to inadequate EEG/EMG recordings.…”

Section: Experiments 1: Icv Hcrt-1supporting

confidence: 88%

“…Two animals were excluded from these analyses due to inadequate EEG/EMG recordings. As previously described (España et al, 2001), the highest dose of HCRT-1 (0.7 nmol, n ¼ 6) significantly increased the time spent awake for approximately 120 min, while the lower dose (0.07 nmol, n ¼ 5) elicited a shorter-duration increase in waking (data not shown). Vehicle infusion (n ¼ 5) did not alter the time spent awake.…”

Section: Experiments 1: Icv Hcrt-1supporting

confidence: 79%

“…To characterize the effects of HCRT-1 on extracellular levels of DA within the PFC, dialysis samples were collected from the medial PFC (Figures 1 and 2a) prior to and after ICV infusions of either vehicle (n ¼ 6) or HCRT-1 (0.07 nmol, n ¼ 6; 0.7 nmol, n ¼ 6). These doses were chosen based on previous studies demonstrating the dose-dependent wake-promoting actions of ICV HCRT-1 across this dose range (España et al, 2001). HCRT-1 dose-dependently increased DA levels in PFC dialysate samples (treatment F 2,15 ¼ 11.90, Po0.001; time F 9,135 ¼ 16.53, Po0.001; treatment Â time interaction F 18,135 ¼ 3.07, Po0.001).…”

Section: Experiments 1: Icv Hcrt-1mentioning

confidence: 99%

“…These peptides have been implicated in the regulation of behavioral state and statedependent processes. For example, central administration of HCRT-1 exerts potent wake-promoting actions (Piper et al, 2000;España et al, 2001). Moreover, dysregulated HCRT neurotransmission is associated with the sleep/ arousal disorder narcolepsy (for reviews, see Hungs and Mignot, 2001;Scammell, 2001).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Experiments 1: Icv Hcrt-1supporting

confidence: 88%

Section: Experiments 1: Icv Hcrt-1supporting

confidence: 79%

Section: Experiments 1: Icv Hcrt-1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Microinjections of orexin directly into the LC (Bourgin et al, 2000), TMN (Huang et al, 2001), BF cholinergic area (Espana et al, 2001), LDT (Xi et al, 2001), and lateral preoptic area (Methippara et al, 2000) has arousal effects similar to those of ICV injection on sleep/wakefulness states. Recent optogenetic and pharmacogenetic manipulations of orexin neurons established a definite causal relation between their neuronal activities and transitions of sleep/wakefulness states (Adamantidis et al, 2007;Sasaki et al, 2011;Tsunematsu et al, 2011).…”

Section: Mmandtsmentioning

confidence: 90%

Overview of orexin/hypocretin system

Mieda

Sakurai

2012

Progress in Brain Research

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A series of recent studies has established the orexin/hypocretin system as a critical regulator of sleep/wake states. Its deficiency results in the sleep disorder narcolepsy in humans, dogs, and rodents. These findings have brought about the possibility of novel therapies for sleep disorders including narcolepsy and insomnia. Moreover, accumulating evidence indicates that the orexin/hypocretin system regulates sleep and wakefulness through interactions with neuronal systems that regulate emotion, reward, and energy homeostasis. Here, we briefly summarize the progress of orexin/hypocretin studies and future perspectives.

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Hypocretin/Orexin System

Sutcliffe

Lecea

2007

Handbook of Contemporary Neuropharmacology

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The hypocretins (also called the orexins) are excitatory neurotransmitters produced in a few thousand neurons of the lateral hypothalamus. Two G protein‐coupled receptors for the hypocretins have different distributions within the CNS and differential affinities for the two hypocretin peptides. Hypocretins efferents project to areas within the posterior hypothalamus that are implicated in feeding behaviors and hormone secretion. Hypocretin fibers also project to diverse targets in other brain regions and the spinal cord, including several areas implicated in cardiovascular function and sleep‐wake regulation. Administration of the hypocretins stimulates food intake, affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement (REM) sleep. Narcolepsy is a disorder of the hypocretin system. One aspect of hypocretin activity is the direct excitation of cholinergic forebrain neurons, brainstem monoaminergic REM‐off neurons in the locus coeruleus and dorsal raphe nucleus, and histaminergic tuberomammillary nucleus, which together suppress slow‐wave sleep. The hypocretins also modulate the activity of cholinergic REM‐on neurons in the brainstem, which gate REM entry.

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Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action

Cited by 292 publications

References 50 publications

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

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

Overview of orexin/hypocretin system

Hypocretin/Orexin System

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