Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats

Akanmu, Moses A.; Honda, Kazuo

doi:10.1016/j.brainres.2005.04.064

Cited by 73 publications

(68 citation statements)

References 41 publications

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“…Consistent with this thesis, fragmentation of wakefulness in OX 2 R −/− mice is milder than that in OX 1 R −/− ;OX 2 R −/− mice (Sakurai, 2007). In addition, ICV administration of an OX 2 Rselective agonist [Ala 11 ]orexin-B seemed less effective when compared with orexin-A (Akanmu and Honda, 2005). However, ICV administration of orexin-A in OX 2 R-deficient dogs has been reported to have no effect on time spent in wakefulness (Fujiki et al, 2003).…”

Section: Discussionsupporting

confidence: 64%

“…A previous pharmacological study using OX 1 Rand OX 2 R-selective antagonists in rats also demonstrated a principal role of OX 2 R in suppression of NREM sleep (Dugovic et al, 2009). Furthermore, ICV administration of an OX 2 R-selective agonist [Ala 11 ]orexin-B in rats was sufficient to promote wakefulness and suppress NREM and REM sleep (Akanmu and Honda, 2005).…”

Section: Discussionmentioning

confidence: 81%

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Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep

Hasegawa

Mieda

Kisanuki

et al. 2011

Neuroscience Research

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Orexin-A and orexin-B are hypothalamic neuropeptides that play critical roles in the maintenance of wakefulness. Intracerebroventricular (ICV) administration of orexin-A has been shown to promote wakefulness and suppress both rapid eye movement (REM) sleep and non-REM (NREM) sleep through the orexin receptor-1 (OX 1 R) and orexin receptor-2 (OX 2 R). Here, we elucidated the differential roles of orexin receptors in the regulation of sleep and wakefulness by comparing the effects of ICV orexin-A administration in wild-type, OX 1 R −/− , and OX 2 R −/− mice. The effects of orexin-A on wakefulness and NREM sleep were significantly attenuated in both knock-out mice as compared with wild-type mice, with substantially larger attenuation in OX 2 R −/− mice than in OX 1 R −/− mice. These results suggest that although the OX 2 R-mediated pathway has a pivotal role in the promotion of wakefulness, OX 1 R also plays additional roles in promoting arousal. In contrast, suppression of REM sleep by orexin-A administration was slightly and similarly attenuated in both OX 1 R −/− and OX 2 R −/− mice, suggesting a comparable contribution of the two receptors to REM sleep suppression. Histological studies demonstrated differential distributions of each receptor subtype in distinct neuronal populations with specific neurotransmitter identities in brainstem cholinergic/monoaminergic neurons. In the laterodorsal tegmental and pedunculopontine tegmental nuclei especially, cholinergic neurons exclusively expressed OX 1 R mRNA, but OX 2 R mRNA was expressed mainly in GABAergic putative interneurons. Thus, each orexin receptor subtype plays differential roles in gating NREM and REM sleep through distinct neuronal pathways.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 81%

Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep

Hasegawa

Mieda

Kisanuki

et al. 2011

Neuroscience Research

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“…In contrast to the narcoleptic phenotype in dogs and humans with dysfunctional orexin receptors or deficiencies in endogenous peptide ligands, (Lin et al, 1999;Nishino et al, 2000;Peyron et al, 2000;Wu et al, 2002), studies in rodents have demonstrated that intracerebroventricular administration of the orexin ligands serves to induce arousal and increase wakefulness (Hagan et al, 1999;Akanmu and Honda, 2005). Deadwyler et al (2007) further reported that systemic and intranasal delivery of OX-A can decrease the effects of sleep deprivation on cognitive performance in nonhuman primates.…”

Section: A Orexin Receptor Agonists/potentiatorsmentioning

confidence: 99%

“…Intracerebroventricular administration of OX-A, OX-B, or [Ala 11 ]OX-B, a modified signaling peptide having 120-fold selectivity for OX 2 receptors, similarly promote wakefulness and decrease the amount of time spent in REM and slow-wave sleep in a dosedependent manner in rats (Hagan et al, 1999;Akanmu and Honda, 2005). Conversely, OX 2 receptor-selective antagonists have sleep-promoting effects similar to antagonists having equal potencies for both OX 1 and OX 2 receptors, including attenuated active wake, increased REM and NREM sleep, and decreased latencies to NREM and REM (Dugovic et al, 2008).…”

Section: E Role Of Ox 2 Receptors In the Control Of Arousal Vigilanmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

et al. 2012

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“…The animals were maintained at a temperature of 24 ± 1 1C, at a relative humidity of 54 ± 6% and in a light-dark cycle of 12:12 h (lights were turned on at 0900 hours and turned off at 2100 hours). [8][9][10] All experimental protocols were performed in accordance with the Guidelines for Animal Experimentation as stipulated by Tokyo Medical and Dental University.…”

Section: Methods Animalsmentioning

confidence: 99%

A critical role of sympathetic nerve regulation for the treatment of impaired daily rhythm in hypertensive Dahl rats

et al. 2010

Self Cite

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There is a deep relationship between impaired circadian rhythm and hypertension. However, the detailed mechanisms between the daily sleep-wake rhythm and cardiovascular disorders have not yet been elucidated. To clarify the mechanism, we examined salt-sensitive Dahl rats that were fed normal chow (n¼10), high-salt chow (n¼10) and high-salt chow with bisoprolol (n¼10). Simultaneous electroencephalogram, electromyogram and locomotor activity were examined to analyze the sleep-wake state. We also examined heart rate, blood pressure and echocardiographic findings to verify the presence of hypertension. Hypertension with impaired ventricular contraction was observed in the rats with high-salt-chow consumption whereas normal-chow rats did not show these disorders. Although rats with the normal diet showed a standard daily rhythm with normal rapid eye movement (REM) sleep duration and locomotor activity, the high-salt-diet group exhibited an impaired daily rhythm with suppressed REM sleep and significant abnormal locomotor activity. Bisoprolol significantly improved the daily sleep-wake rhythm and locomotor activity. We showed that an impaired daily rhythm was closely related to the development of hypertension. Keywords: b-blocker; daily rhythm; locomotor activity INTRODUCTION It is well known that there is a deep relationship between sleep disorders and cardiovascular diseases such as hypertension and congestive heart failure (CHF). The fact that patients with advanced CHF induced by hypertension frequently suffer from central breathing disorders 1 suggests that CHF is causally related to alterations in the central control of breathing, resulting in Cheyne-Stokes respiration during sleep. 2 Disorders in the central control of breathing are a key factor in altered daily sleep-wake rhythm and are also an independent predictor for premature death. 3,4 Although it is known that cardiovascular diseases are closely related to circadian rhythm, 5 the relationship among changes in circadian rhythm, sleep disorders and cardiovascular diseases has not yet been elucidated.It has been reported that long-term treatment with b-receptorblocking substances (b-blockers) improves hypertension and CHF. bBlockers also reduce the inappropriate increase of ventilation during exercise and alleviate central breathing disorders during wakefulness. 6,7 These positive effects result in improved exercise capacity and slower progression of underlying hypertension and CHF. However, little is known about the effects of b-blocker treatment on sleep

show abstract

Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats

Cited by 73 publications

References 41 publications

Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep

Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

A critical role of sympathetic nerve regulation for the treatment of impaired daily rhythm in hypertensive Dahl rats

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