Orexinergic neurons and barbiturate anesthesia

Kushikata, Tetsuya; Hirota, Kazuyoshi; Yoshida, Hitoshi; Kudo, M; Lambert, David G.; Smart, Darren; Jerman, Jeffrey C.; Matsuki, Akitomo

doi:10.1016/s0306-4522(03)00554-2

Cited by 86 publications

(65 citation statements)

References 40 publications

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“…In addition, we previously reported that intracerebroventricular (i.c.v.) administration of OXs reduced intravenous anesthesia time while OX1 receptor antagonist prolonged it [31,32]. Similarly, Kelts et al [33] reported that genetic ablation of OXergic neurons (OX/ataxin-3 mice) and selective OX1 receptor antagonists delayed emergence from volatile anesthesia such as sevoflurane and isoflurane.…”

Section: Anesthetic Requirementmentioning

confidence: 97%

Sepsis and the orexin system

Hirota

2016

J Anesth

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receptors [10], and are synthesized mainly by neurons located in the posterolateral hypothalamus. OX1 receptors are widely distributed in the central nervous system (CNS), mostly in the ventromedial hypothalamus, and in peripheral tissues such as brown adipose tissue. OX2 receptors are also widely distributed in the CNS, mainly in the paraventricular nucleus, and in peripheral tissues such as the adrenal medulla [11]. The OXergic system plays an important role in several physiological functions such as feeding, sleep-wake cycle, locomotion, thermoregulation, autonomic function including cardiovascular function, and analgesia. OXergic system is particularly known to be involved in the control of the sympathetic nervous system [12]. In addition, the OXergic system contributes to the cardiovascular defense system which is attenuated in OX knockout mice and OX neuron-ablated mice [13]. Pathophysiology of sepsis and the OXergic system Sleep disorderPatients with sepsis in the intensive care unit (ICU) often show complete absence of the normal circadian rhythm pattern. Although rapid eye movement (REM) sleep typically occupies 20-25 % of nocturnal sleep in healthy subjects, patients with sepsis often show an absence or a decrease in REM sleep. It has been suggested that some specific mediators such as endotoxin may disrupt REM sleep [14]. Baracchi et al. [15] reported that septic rats showed suppression of REM sleep and δ-power during non-REM sleep and fragmented sleep during dark periods. Lipopolysaccharide (LPS) infusion significantly decreases OXergic neurons [7][8][9]. LPS infusion at 0.22 μg/h significantly reduced not only OX by 29.7 % but also REM sleep [7]. The sleepwake cycle returns to normal after recovery from sepsis.

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Section: Anesthetic Requirementmentioning

confidence: 97%

Sepsis and the orexin system

Hirota

2016

J Anesth

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“…A preliminary study has demonstrated that a selective antagonist for orexin receptor 1, SB 334867, reverses the arousal-promoting action of orexin A in anesthetized animals [26] . In this study, we further tested the effect of SB 334867 on spontaneous sleep and wakefulness in conscious rats.…”

Section: Orexin a Promotes Arousal Through Activation Of Orexin Recepmentioning

confidence: 99%

Orexin A attenuates the sleep-promoting effect of adenosine in the lateral hypothalamus of rats

et al. 2014

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Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study, electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the fi rst 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h. Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the fi rst 3-h post-injection. No signifi cant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. These findings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1.

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“…Moreover, because of their direct monosynaptic projections throughout the forebrain, activation of orexinergic neurons stabilizes wakefulness. Genetic and pharmacologic blockade of orexin-mediated signaling impairs arousal (12)(13)(14)(15)(16). Two parallel lines of evidence suggest that orexin signaling can modify the anesthetic state, with orexin agonists decreasing anesthetic duration and an orexin-1 receptor antagonist, SB-334867-A, increasing anesthetic duration (13,17).…”

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confidence: 99%

“…Genetic and pharmacologic blockade of orexin-mediated signaling impairs arousal (12)(13)(14)(15)(16). Two parallel lines of evidence suggest that orexin signaling can modify the anesthetic state, with orexin agonists decreasing anesthetic duration and an orexin-1 receptor antagonist, SB-334867-A, increasing anesthetic duration (13,17). Because hypersensitivity to induction of anesthesia and delayed emergence from anesthesia could independently alter anesthetic duration, we sought to provide a direct link of orexin signaling on anesthetic induction and emergence.…”

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confidence: 99%

An essential role for orexins in emergence from general anesthesia

Kelz

Sun

Chen

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

298

280

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The neural mechanisms through which the state of anesthesia arises and dissipates remain unknown. One common belief is that emergence from anesthesia is the inverse process of induction, brought about by elimination of anesthetic drugs from their CNS site(s) of action. Anesthetic-induced unconsciousness may result from specific interactions of anesthetics with the neural circuits regulating sleep and wakefulness. Orexinergic agonists and antagonists have the potential to alter the stability of the anesthetized state. In this report, we refine the role of the endogenous orexin system in impacting emergence from, but not entry into the anesthetized state, and in doing so, we distinguish mechanisms of induction from those of emergence. We demonstrate that isoflurane and sevoflurane, two commonly used general anesthetics, inhibit c-Fos expression in orexinergic but not adjacent melaninconcentrating hormone (MCH) neurons; suggesting that wakeactive orexinergic neurons are inhibited by these anesthetics. Genetic ablation of orexinergic neurons, which causes acquired murine narcolepsy, delays emergence from anesthesia, without changing anesthetic induction. Pharmacologic studies with a selective orexin-1 receptor antagonist confirm a specific orexin effect on anesthetic emergence without an associated change in induction. We conclude that there are important differences in the neural substrates mediating induction and emergence. These findings support the concept that emergence depends, in part, on recruitment and stabilization of wake-active regions of brain.anesthetic hypnosis ͉ arousal ͉ narcolepsy ͉ NREM sleep circuits ͉ volatile anesthetics

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Orexinergic neurons and barbiturate anesthesia

Cited by 86 publications

References 40 publications

Sepsis and the orexin system

Sepsis and the orexin system

Orexin A attenuates the sleep-promoting effect of adenosine in the lateral hypothalamus of rats

An essential role for orexins in emergence from general anesthesia

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