Evidence for histaminergic arousal mechanisms in the hypothalamus of cat

Lin, Jian‐Sheng; Sakai, Kazuya; Jouvet, Michel

doi:10.1016/0028-3908(88)90159-1

Cited by 307 publications

(137 citation statements)

References 39 publications

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“…Histaminergic pathways originating from the reticular formation project diffusely to the cerebral cortex in a similar way to monoaminergic pathways concerned with alertness (Garbarg et al, 1980;Pollard & Schwartz, 1987). Further, administration of histamine or drugs which enhance histaminergic transmission leads to desynchronization of the EEG and wakefulness (Wolf & Monnier, 1973;Monti et al, 1986;Lin et al, 1988), and histamine may also modulate the activity of medullary neurones (Jones et al, 1983;Bradley et al, 1984). Circadian rhythms in the level of histamine have been found in various regions of the brain (Friedman & Walker, 1968;Orr & Quay, 1975), and the rate of formation of histamine is elevated in rodents during the period of darkness when spontaneous activity is maximal (Schwartz et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

Sedation and histamine H₁‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Nicholson

Pascoe

Turner

et al. 1991

British J Pharmacology

118

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1 The effects of 10mg (+)-and (-)-chlorpheniramine and 5mg (+)-and (-)-dimethindene on daytime sleep latencies, digit symbol substitution and subjective assessments of mood and well-being were studied in 6 healthy young adult humans. Each subject also took 5mg triprolidine hydrochloride as an active control and two placebos. 2 Daytime sleep latencies were reduced with triprolidine, (+)-chlorpheniramine and (-)-dimethindene, and subjects also reported that they felt more sleepy after (+)-chlorpheniramine and (-)-dimethindene. Performance on digit symbol substitution was impaired with (+ )-chlorpheniramine. 3 Changes in measures with (-)-chlorpheniramine and (+)-dimethindene were not different from changes with placebo. 4 In the present study, changes in measures of drowsiness and performance were limited to the enantiomers with high affinity for the histamine Hl-receptor. These findings strongly suggest that sedation can arise from H1-receptor antagonism alone, and provide further support for the belief that the histaminergic system is concerned with the regulation of alertness in man.

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Section: Discussionmentioning

confidence: 99%

Sedation and histamine H₁‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Nicholson

Pascoe

Turner

et al. 1991

British J Pharmacology

118

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“…Among these brain regions, the TMN is thought to be the center for the site of action of orexin-induced arousal. Because histaminergic TMN neurons are implicated in arousal (Lin et al, 1988;Monti, 1993), they fire tonically during wakefulness (Steininger et al, 1999) and are activated by orexin via the OX2R (Bayer et al, 2001;Eriksson et al, 2001;Yamanaka et al, 2002). In addition, the effect of orexin on arousal was not observed in histamine 1 receptor knock-out (H1 Ϫ/Ϫ ) mice (Huang et al, 2001).…”

Section: Physiological Significance Of Orexininduced Activation Of Ormentioning

confidence: 99%

“…OX2R mRNA has been shown to be prominent in the cerebral cortex, septal nuclei, hippocampus, and hypothalamic nuclei, including the histaminergic tuberomammillary nucleus (TMN) (Marcus et al, 2001). Among these brain regions, the TMN is thought to be the center for the site of action of orexin-induced arousal, because histaminergic TMN neurons are implicated in arousal (Lin et al, 1988;Monti, 1993). The TMN neurons fire tonically during wakefulness (Steininger et al, 1999) and are activated by orexin via OX2R (Bayer et al, 2001;Eriksson et al, 2001;Yamanaka et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor

Yamanaka¹,

Tabuchi²,

Tsunematsu³

et al. 2010

J. Neurosci.

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Orexin neurons (hypocretin neurons) have a critical role in the regulation of sleep/wakefulness, especially in the maintenance of arousal. Here, we revealed that orexin neurons are directly and indirectly activated by orexin via the orexin 2 receptor (OX2R). Orexin B (1 M) induced depolarization in orexin neurons, which was still observed in the presence of TTX (1 M), AP-5 (50 M), and CNQX (20 M). In addition, orexin B induced inward currents in the presence of TTX, suggesting a direct activation of orexin neurons. Although orexin B application induced depolarization in orexin neurons of OX1R knock-out mice at comparable levels to wild-type mice, the observation that orexin B failed to depolarize orexin neurons in the OX2R knock-out mice suggested that OX2R was a primary receptor for this response. Moreover, immunoelectron microscopic analyses revealed direct contacts among orexin neurons, which exhibited structural similarities to the glutamatergic synapses. Together, these results suggest that orexin neurons form a positive-feedback circuit through indirect and direct pathways, which results in the preservation of the orexin neuron network at a high activity level and/or for a longer period. Therefore, the activation of orexin neurons through OX2R might have an important role in the maintenance of arousal.

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“…Approximately 80% of the neurons in this population contain the inhibitory neurotransmitters GABA and galanin. Histaminergic neurons in the TMN are believed to play a key role in promoting wakefulness (Lin et al, 1988(Lin et al, , 1996Steininger et al, 1999); inhibition of these neurons by the VLPO is thought to play a major role in causing sleep. Steininger et al (1997) and Yang and Hatton (1997) have shown that electrical stimulation in the VLPO region causes GABA A receptor-mediated hyperpolarization and inhibition of TMN neurons in brain slices.…”

Section: Abstract: Preoptic Area; Hypothalamus; Rem Sleep; Nrem Sleementioning

confidence: 99%

Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep

Lü¹,

et al. 2000

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Neurons in the ventrolateral preoptic nucleus (VLPO) in rats show c-fos activation after sleep and provide GABAergic innervation of the major monoamine arousal systems, suggesting that they may be a necessary part of the brain circuitry that produces sleep. We examined the effects on sleep behavior in rats of cell-specific damage to the VLPO by microinjection of ibotenic acid. Severe lesions of the central cell cluster of the VLPO (ϳ80-90% cell loss bilaterally) caused a 60-70% decrease in delta power and a 50-60% decrease in nonrapid-eyemovement (NREM) sleep time ( p Ͻ 0.001). The number of remaining Fos-immunoreactive neurons in the VLPO cell cluster was linearly related to NREM sleep time (r ϭ 0.77; p Ͻ 0.001) and total electroencephalogram delta power (r ϭ 0.79; p Ͻ 0.001) but not to rapid-eye-movement (REM) sleep (r ϭ 0.35; p Ͼ 0.10). Lesions in the region containing scattered VLPO neurons medial or dorsal to the cell cluster caused smaller changes in NREM sleep time (24.5 or 15%, respectively) but were more closely associated with loss of REM sleep (r ϭ 0.74; p Ͻ 0.01). The insomnia caused by bilateral VLPO lesions persisted for at least 3 weeks. Lesions of the VLPO caused no change in mean body temperature or its circadian variation; after small lesions of the ventromedial preoptic nucleus, body temperature showed normal circadian variation but a wider temperature range, and sleep behavior was not affected. These experiments delineate distinct preoptic sites with primary effects on the regulation of NREM sleep, REM sleep, and body temperature. Key words: preoptic area; hypothalamus; REM sleep; NREM sleep; thermoregulation; circadian rhythmsThe involvement of the preoptic area and adjacent basal forebrain in sleep regulation has been recognized since von Economo (1930) reported that lesions of this region cause prolonged insomnia in humans. Nauta (1946) demonstrated that preopticbasal forebrain lesions cause insomnia in rats, and Sterman and Clemente (1962a,b) demonstrated similar effects in cats. These experimental studies used electrolytic or mechanical lesions that not only destroyed neuronal cell bodies but also damaged fibers of passage. More recent studies using chemical toxins to ablate the neuronal cell bodies in this area in rats and cats have confirmed the production of insomnia (Szymusiak and McGinty, 1986;Sallanon et al., 1989;John and Kumar, 1998). However, these studies used large lesions and hence could not identify a specific neuronal population that was responsible for the deficit in sleep regulation.Recently, Sherin et al. (1996) identified a specific population of neurons in the ventrolateral preoptic nucleus (VLPO) that show Fos immunoreactivity after sleep (sleep-positive neurons). The number of Fos-immunoreactive (-IR) neurons in this region was directly proportional to the number of minutes of sleep during the previous hour (Sherin et al., 1996), in good agreement with electrophysiological studies showing that sleep-active neurons, with firing rates two to three times faster during...

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Evidence for histaminergic arousal mechanisms in the hypothalamus of cat

Cited by 307 publications

References 39 publications

Sedation and histamine H₁‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Sedation and histamine H₁‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor

Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep

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Evidence for histaminergic arousal mechanisms in the hypothalamus of cat

Cited by 307 publications

References 39 publications

Sedation and histamine H1‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Sedation and histamine H1‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Orexin Directly Excites Orexin Neurons through Orexin 2 Receptor

Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep

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Sedation and histamine H₁‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

Sedation and histamine H₁‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene