Histaminergic modulation of neocortical spindling and slow-wave activity in freely behaving rats

Valjakka, Antti; Vartiainen, Jukka; Kosunen, H.; Hippeläinen, Mikko; Pesola, P.; Olkkonen, H.; Airaksinen, Mauno M.; Tuomisto, Leena

doi:10.1007/bf01271187

Cited by 17 publications

(14 citation statements)

References 51 publications

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“…12,17 Furthermore, the spontaneous, as well as the depolarizationinduced and pharmacologically induced histamine release from anterior hypothalamus are significantly increased in these rats. 17 Histamine, through the activation of postsynaptic H 1 receptors, is involved in the regulation of the mechanisms of arousal, 19,20 locomotor activity, [21][22][23][24] feeding behavior, and energy balance, 25,26 and circadian rhythmicity (for reviews, see Tuomisto 27 and Nowak 28 ). We have previously suggested that histaminergic synaptic imbalance may have contributed to the sleep disturbances in rats with PCA.…”

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Effects of the histamine H1 receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

et al. 2000

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To find out whether the changes in the brain histaminergic system are involved in the pathophysiology of portalsystemic encephalopathy, we examined the effects of histamine H 1 receptor blockade on spontaneous locomotor activity, feeding, and circadian rhythmicity in rats with portacaval anastomosis (PCA). Pyrilamine, an H 1 receptor blocker (15 mg/kg/day), was delivered with osmotic minipumps. Spontaneous locomotor activity was recorded for 72 hours in the open-field with an electromagnetic detector. Food intake was monitored twice daily at the end of the light (7 PM) and the dark (7 AM) phases for 3 days. Histamine H 1 receptor density in the suprachiasmatic nucleus (SCN) was examined with receptor autoradiography, employing [ 3 H]pyrilamine. PCA surgery led to decreased movement time and velocity and flattened amplitude of the circadian rhythms of locomotion and feeding. In sham-operated rats, pyrilamine significantly decreased the movement time and velocity, as well as the total food consumption and completely abolished the circadian rhythmicity of locomotion. In contrast, pyrilamine increased the movement time and velocity in PCA-operated rats, particularly in the dark phase, and improved the precision of the circadian rhythms of locomotion and feeding. Histamine H 1 receptor density was not altered by PCA surgery, whereas pyrilamine treatment led to the complete blockade of H 1 receptors in both sham-and PCA-operated rats. We suggest that histaminergic imbalance has contributed to the generation and maintenance of the decreased spontaneous locomotor activity and altered circadian rhythmicity following PCA surgery in the rat, probably via an H 1 receptor-mediated mechanism. (HEPATOL-OGY 2000;31:336-344.)Animal models of human disease provide the means of studying the pathological condition in a way that is not always possible in human patients. The rat with an end-toside portacaval anastomosis (PCA) represents an attractive model of portal-systemic encephalopathy (PSE) 1,2 because many of the behavioral abnormalities that occur in this model correspond to the subclinical forms of PSE. Among these abnormalities are the significantly reduced spontaneous locomotor activity and exploration, 3 as well as the reduced or completely abolished differences between day time and night time activity, suggesting a disruption of their circadian rhythmicity. 4-10 These rats also have disturbances in their food intake 11 and show marked growth retardation. 12 Although much research has been performed to elucidate the pathophysiological background of PSE, the exact mechanisms that underlie this condition are still largely unclear. PSE has been described as a disorder of multiple neurotransmitter systems. 13 Specifically, the histaminergic synaptic imbalance, which becomes apparent shortly 14,15 and persists for at least 8 months after surgery, 12,16-18 is among the most interesting consequences of portacaval shunting in the rat.We have previously shown that rats with PCA have profound disturbances in their brain histaminergi...

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Effects of the histamine H1 receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

et al. 2000

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“…9,11 One of the most striking consequences of the PCA surgery in rats is the remarkable elevation of brain histamine levels, which appears as early as 10 days, and persists for at least 8 months after PCA surgery. [12][13][14][15] The significance of this observation for the pathogenesis of PSE, however, has not been studied in detail.Histaminergic neurons in the mammalian brain are thought to play a role in the control of vigilance, sleep, and wakefulness, [16][17][18][19][20][21] and in the modulation of circadian rhythmicity. 22 The role of histaminergic mechanisms in the control of the sleep-wakefulness continuum in humans has also been confirmed.…”

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“…23,24 Furthermore, earlier studies have demonstrated a correlation between the sleep disturbances and brain histamine levels in rats with PCA. 21,25 Because histamine has a well-known physiological role in the modulation of sleep behavior and circadian rhythms, we have now attempted to find out whether the increased brain levels of histamine in PCA-operated rats are associated with changes in the sleep patterns of these rats during the light phase. Because such changes cannot be detected by simple observation, we used electroencephalographic (EEG) recordings from the frontal cortex of freely behaving rats as brain-state markers to discriminate sleep, drowsiness, and wakefulness.…”

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“…18 The spindle bursts, identified as rhythmic waves of 5 to 10 Hz with spike-and-wave pattern, were thought to signify drowsiness. 21 To discover the short-term and the Abbreviations: PSE, portal-systemic encephalopathy; PCA, portacaval anastomosis; EEG, electroencephalography; 5-HT, 5-hydroxytryptamine (serotonin); 5-HIAA, 5-hydroxyindole-3-acetic acid.From the …”

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“…Histaminergic neurons in the mammalian brain are thought to play a role in the control of vigilance, sleep, and wakefulness, [16][17][18][19][20][21] and in the modulation of circadian rhythmicity. 22 The role of histaminergic mechanisms in the control of the sleep-wakefulness continuum in humans has also been confirmed.…”

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Brain Histamine Levels and Neocortical Slow–Wave Activity in Rats With Portacaval Anastomosis

et al. 1999

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To determine whether the increased histamine levels in the brain of rats with portacaval anastomosis (PCA) are associated with the development of sleep disturbances during the light phase, the neocortical slow-wave activity of PCA-operated rats was examined with electroencephalography (EEG) 1 month and 6 months after the surgery. The tissue levels of histamine, tele-methylhistamine, 5-hydroxytryptamine (5-HT) (serotonin), and 5-hydroxyindole-3-acetic acid (5-HIAA) in frontal cortex were assayed by high-performance liquid chromatography 6 months after the surgery. PCA surgery led to changes in the synchronized, low-frequency, high-amplitude frontal cortex EEG activity recorded during the light phase. Delta-wave amplitude but not delta time was significantly decreased, whereas both spindle amplitude and spindling time were significantly decreased. There were also significant age-related changes, presented as increases in the duration of spindles and the amplitude of both delta waves and spindles. PCA-operated rats showed a change in the pattern of EEG activity with increasing age similar to sham-operated rats. This suggests that once established, the resetting of the systems regulating the sleep-waking behavior is being maintained with time. The tissue levels of both histamine and metabolite in the frontal cortex were increased, whereas the serotonin system showed only an increase in the level of the metabolite. There was a significant negative correlation between the spindling time and the tissue histamine levels. We suggest that histamine, which participates in the control of vigilance, sleep, and wakefulness, as well as in the modulation of circadian rhythmicity, may play a role in the development of sleep disturbances in rats with PCA. (HEPATOLOGY 1999;29:340-346.)Portal-systemic encephalopathy (PSE) is a potential longterm complication in any patient with chronic liver disease receiving a portacaval shunt. The biochemical changes that occur in the plasma and brain of patients with PSE can be reproduced in the rat with portacaval anastomosis (PCA). 1 The clinical presentation of PSE at early stages is dominated by the diminished total duration of slow-wave sleep, the disorganization of the normal nocturnal sleep cycles, the reversed sleep patterns, and the decrease in the spontaneous voluntary movement. Moreover, according to a recent study, approximately half of the cirrhotic patients without overt encephalopathy complain of sleep disturbances. 2 The neurological changes that are consequences of a portacaval shunt in the rat are also manifested as disruptions of sleep patterns and diurnal rhythms, changes in the vigilance or motor activity, and neuromuscular coordination. [3][4][5][6][7][8][9][10] Although much research has been performed to reveal the pathogenesis of PSE, the exact mechanisms responsible for the generation and maintenance of the sleep disturbances are still unclear. Until now, they have been attributed mainly to modification of serotonergic neurotransmission. 9,11 One of the most striking co...

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Brain histamine in the WAG/Rij rat, an animal model of absence epilepsy

Midzyanovskaya¹,

Kuznetsova²,

Tuomisto³

2002

Inflamm. res.

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Histaminergic modulation of neocortical spindling and slow-wave activity in freely behaving rats

Cited by 17 publications

References 51 publications

Effects of the histamine H1 receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Effects of the histamine H1 receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Brain Histamine Levels and Neocortical Slow–Wave Activity in Rats With Portacaval Anastomosis

Brain histamine in the WAG/Rij rat, an animal model of absence epilepsy

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