Publications

State-dependent changes in cortical gain control as measured by auditory evoked responses to varying intensity stimuli.	Auditory evoked potential (AEP) components correspond to sequential activation of brain structures within the auditory pathway and reveal neural activity during sensory processing. To investigate state-dependent modulation of stimulus intensity response profiles within different brain structures, we assessed AEP components across both stimulus intensity and state.	2011	22043124
Synthesis and evaluation of pyridone-phenoxypropyl-R-2-methylpyrrolidine analogues as histamine H3 receptor antagonists.	6-{4-[3-(R)-2-Methylpyrrolidin-1-yl)propoxy]-phenyl}-2H-pyridazin-3-one 6 (Irdabisant; CEP-26401) was recently reported as a potent H(3)R antagonist with excellent drug-like properties and in vivo activity that advanced into clinical evaluation. A series of pyridone analogs of 6 was synthesized and evaluated as H(3)R antagonists. Structure-activity relationships revealed that the 5-pyridone regiomer was optimal for H(3)R affinity. N-Methyl 9b showed excellent H(3)R affinity, acceptable pharmacok ...	2011	22014551
[Selective stimulations and lesions of the rat brain nuclei as the models for research of the human sleep pathology mechanisms].	Many complex behavioral phenomena such as sleep can not be explained without multidisciplinary experimental approach, and complementay approaches in the animal models "in vivo" and human studies. Electrophysiological, pharmacological, anatomical and immunohistochemical techniques, and particularly stereotaxically guided local nanovolume microinjection technique, enable us to selectively stimulate and lesion the brain nuclei or their specific neuronal subpopulation, and to reslove the mechanisms ...	2011	22165729
Synthesis and structure-activity relationship of 5-pyridazin-3-one phenoxypiperidines as potent, selective histamine H(3) receptor inverse agonists.	Optimization of the R(2) and R(6) positions of (5-{4-[3-(R)-2-methylpyrrolin-1-yl-propoxy]phenyl}-2H-pyridazin-3-one) 2a with constrained phenoxypiperidines led to the identification of 5-[4-(cyclobutyl-piperidin-4-yloxy)-phenyl]-6-methyl-2H-pyridazin-3-one 8b as a potent, selective histamine H(3) receptor antagonist with favorable pharmacokinetic properties. Compound 8b had an excellent safety genotoxocity profile for a CNS-active compound in the Ames and micronucleus tests, also displayed pote ...	2011	22197136
social partnering significantly reduced rapid eye movement sleep fragmentation in fear-conditioned, stress-sensitive wistar-kyoto rats.	negative emotionality affects sleep-wake behavior in humans and rodents, and the wistar-kyoto (wky) rat strain is known for its stress-sensitive phenotype. analyzing rapid eye movement sleep (rems) microarchitecture by separating rems into single (sirems; inter-rem episode interval>3 min) and sequential (seqrems; interval≤3 min) episodes, we previously reported that cued fear conditioning (cfc) increased rems fragmentation in wky compared to wistar rats by increasing the number of seqrems episod ...	2011	22015926
differential distribution of melanin-concentrating hormone (mch)- and hypocretin (hcrt)-immunoreactive neurons projecting to the mesopontine cholinergic complex in the rat.	hypocretin (hcrt or orexin) and melanin-concentrating hormone (mch) containing neurons are located in the hypothalamus and are implicated in the regulation of feeding behavior, energy homeostasis, and sleep-wake cycle. mch and hcrt are not co-localized within the same neuron, but these neurons project widely throughout the brain, especially to brain regions regulating arousal. recent data indicate that hcrt and mch neurons located medially with respect to the fornix have a differential projectio ...	2011	22015351
ischemic stroke selectively inhibits rem sleep of rats.	sleep disorders are important risk factors for stroke; conversely, stroke patients suffer from sleep disturbances including disruptions of non-rapid eye movement (nrem) and rapid eye movement (rem) sleep and a decrease in total sleep. this study was performed to characterize the effect of stroke on sleep architecture of rats using continuous electroencephalography (eeg) and activity monitoring. rats were implanted with transmitters which enabled continuous real time recording of eeg, electromyog ...	2011	21906592
sleep-related epilepsy in a long-evans hooded rat model of depression.	introduction: neonatal treatment with clomipramine (cli) has been shown to have reliable behavioral and biological changes that mimic major symptomatic and biochemical changes found in depression. this paper further explores a common feature of depression, the comorbidity of seizure activity and depressive behaviors in this mode. methods: rat pups were neonatally treated with 40 mg/kg/day of cli from postnatal da ...	2011	22205358
evaluation of periodic limb movements in a putative animal model of restless leg syndrome.	restless leg syndrome (rls) is a major healthcare burden with increasing prevalence. it has been demonstrated that periodic limb movements (plm) can occur as an isolated phenomenon, but they are often associated with this syndrome and are the only symptom of this disorder that can be measured electrophysiologically. the aim of this study was to examine the sleep-wake behavior and the presence of limb movement in a rat model of rls induced by lesioning the a11 dopaminergic nuclei with the neuroto ...	2011	22162115
modulation of fronto-cortical activity by modafinil: a functional imaging and fos study in the rat.	modafinil (mod) is a wake-promoting drug with pro-cognitive properties. despite its increasing use, the neuronal substrates of mod action remain elusive. in particular, animal studies have highlighted a putative role of diencephalic areas as primary neuronal substrate of mod action, with inconsistent evidence of recruitment of fronto-cortical areas despite the established pro-cognitive effects of the drug. moreover, most animal studies have employed doses of mod of limited clinical relevance. we ...	2011	22048464
synthesis and evaluation of pyridazinone-phenethylamine derivatives as selective and orally bioavailable histamine h3 receptor antagonists with robust wake-promoting activity.	a series of pyridazinone-phenethylamine derivatives with moderate to low nanomolar affinity for rat and human h(3)r are described. these analogs exhibited excellent selectivity and metabolic stability, with acceptable rat pharmacokinetic properties. in vivo, 7 and 11 demonstrated potent h(3)r functional antagonism in the rat dipsogenia model and robust wake-promoting activity in the rat electroencephalogram/electromyography (eeg/emg) model.	2011	21944855
Assessment of network States: local hemodynamics.	Neural activity utilizes energy resources and requires replenishment of metabolites through vascular dilation. During wake, cortical neurons usually have depolarized membrane potentials and exhibit frequent spontaneous action potentials, requiring an increased metabolic delivery to activated tissue and causing blood vessels to dilate. Quiet sleep (QS) is characterized by alternating membrane potential between a depolarized and hyperpolarized state. The hyperpolarized state has a lower membrane p ...	2011	21906020
Differences between Physostigmine- and Yohimbine-induced States Are Visualized in Canonical Space Constructed from EEG during Natural Sleep-wake Cycle in Rats.	Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8. ...	2011	22110362
cortical evoked responses associated with arousal from sleep.	to determine if low-level intermittent auditory stimuli have the potential to disrupt sleep during 24-h recordings, we assessed arousal occurrence to varying stimulus intensities. additionally, if stimulus-generated evoked response potential (erp) components provide a metric of underlying cortical state, then a particular erp structure may precede an arousal.	2011	21203374
Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus.	Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal ...	2011	21880863
Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep-regulating brain regions of Sprague Dawley rat.	Buprenorphine, a partial µ-opioid receptor agonist and ?-opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine concentrations in regions of the basal forebrain and pontine brainstem that regulate sleep.	2011	21857500
Ingestion analgesia occurs when a bad taste turns good.	During ingestion of water, chocolate, sucrose, and saccharin, pain-related behaviors are suppressed. This ingestion analgesic effect is reversed when the hedonic valence of a food is switched from "good" to "bad" as occurs during conditioned taste aversion. Here, we tested the converse hedonic shift to determine if ingestion analgesia occurs when 0.3 M NaCl is made palatable by inducing a sodium appetite. In Experiment 1, sham- and sodium-depleted rats were tested for paw withdrawal and lick lat ...	2011	21928874
delta oscillations induced by ketamine increase energy levels in sleep-wake related brain regions.	neuronal signaling consumes much of the brain energy, mainly through the restoration of the membrane potential (mp) by atp-consuming ionic pumps. we have reported that, compared with waking, atp levels increase during the initial hours of natural slow-wave sleep, a time with prominent electroencephalogram (eeg) delta oscillations (0.5-4.5 hz). we have hypothesized that there is a delta oscillation-atp increase coupling, since, during delta waves, neurons exhibit a prolonged hyperpolarizing phase ...	2011	21958867
c-fos expression in neurons projecting from the preoptic and lateral hypothalamic areas to the ventrolateral periaqueductal gray in relation to sleep states.	the ventrolateral division of the periaqueductal gray (vlpag) and the adjacent deep mesencephalic reticular nucleus have been implicated in the control of sleep. the preoptic hypothalamus, which contains populations of sleep-active neurons, is an important source of afferents to the vlpag. the perifornical lateral hypothalamus (lh) contains populations of wake-active neurons and also projects strongly to the vlpag. we examined nonrem and rem sleep-dependent expression of c-fos protein in preopti ...	2011	21601616
the histamine h3 receptor: from discovery to clinical trials with pitolisant.	the third histamine receptor was discovered in 1983 by a traditional pharmacological approach, consisting of assessing the inhibitory effect of histamine on its own release from depolarized rat brain slices. the same in vitro test was used to design, in 1987, the first highly selective and potent h3-autoreceptor ligands, the antagonist thioperamide and the agonist (r)alphamethylhistamine which enhances and inhibits, respectively, the activity of histaminergic neurons in brain. the use of these r ...	2011	21615387
gene expression and protein distribution of orexins and orexin receptors in rat retina.	orexins, composed of orexin a and orexin b, are identified as endogenous ligands of two orphan g-protein-coupled receptors: orexin 1 and orexin 2 receptors (ox(1)r and ox(2)r). orexins are implicated in regulating wake/sleep states, feeding behaviors, etc. using reverse transcription-polymerase chain reactive (rt-pcr) analysis and immunofluorescence double labeling, we investigated the distributions of orexin a, orexin b, ox(1)r and ox(2)r in rat retina. rt-pcr analysis revealed the presence of ...	2011	21621592
promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.	abstract: orexins/hypocretins are key neuropeptides responsible for regulating central arousal and reward circuits. two receptors respond to orexin signaling, orexin 1 receptor (ox(1)r) and orexin 2 receptor (ox(2)r) with partially overlapping nervous system distributions. genetic studies suggest orexin receptor antagonists could be therapeutic for insomnia and other disorders with disruptions of sleep and wake. suvorexant (mk-4305) is a potent, selective, and orally bioavailable antagonist of o ...	2011	21473737
deep sleep and parietal cortex gene expression changes are related to cognitive deficits with age.	age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging.	2011	21483696
angiotensin i-converting enzyme (ace) activity and expression in rat central nervous system after sleep deprivation.	abstract proteases are essential either for the release of neuropeptides from active or inactive proteins or for their inactivation. neuropeptides have a fundamental role in sleep-wake cycle regulation and their actions are also likely to be regulated by proteolytic processing. using fluorescence resonance energy transfer substrates, specific protease inhibitors and real-time pcr we demonstrate changes in angiotensin i-converting enzyme (ace) expression and proteolytic activity in the central ne ...	2011	21495912
one hundred years of migraine research: major clinical and scientific observations from 1910 to 2010.	(headache 2011;51:752-778) pain research, and headache research in particular, during the 20th century, has generated an enormous volume of literature promulgating theories, questions, and temporary answers. this narrative review describes the most important events in the history of migraine research between 1910 and 2010. based on the standard textbooks of headache: wolff's headache (1948 and 1963) and the headaches (1993, 2000, and 2006) topics were selected for a historical review. most notab ...	2011	21521208
differential effects of nmda antagonists on high frequency and gamma eeg oscillations in a neurodevelopmental model of schizophrenia.	neuroanatomical, electrophysiological and behavioural abnormalities following timed prenatal methylazoxymethanol acetate (mam) treatment in rats model changes observed in post-mortem schizophrenic brains. in particular, mam treatment on gestational day 17 (e17) preferentially disrupts limbic-cortical circuits, and is a promising animal model of schizophrenia. the hypersensitivity of this model to the nmda receptor antagonist-induced hyperactivity has been proposed to mimic the increase in sensit ...	2011	21521646
diaphragm long-term facilitation following acute intermittent hypoxia during wakefulness and sleep.	acute intermittent hypoxia (aih) elicits a form of respiratory plasticity known as long-term facilitation (ltf). here, we tested four hypotheses in unanesthetized, spontaneously breathing rats using radiotelemetry for eeg and diaphragm electromyography (dia emg) activity: 1) aih induces ltf in dia emg activity; 2) diaphragm ltf (dia ltf) is more robust during sleep vs. wakefulness; 3) aih (or repetitive aih) disrupts natural sleep-wake architecture; and 4) preconditioning with daily aih (daih) f ...	2011	21372099
increased non-rapid eye movement sleep by cocaine withdrawal: possible involvement of a2a receptors.	this study attempted to clarify whether cocaine withdrawal altered sleep architecture and the role of adenosine receptors in this process. cocaine (20 mg/kg) was administered subcutaneously once per day for 7 days to rat implanted with sleep/wake recording electrode. polygraphic signs of undisturbed sleep/wake activities were recorded for 24 h before cocaine administration (basal recording as control); withdrawal-day 1 (after 1 day of repeated cocaine administration), withdrawal-day 8 (after 8 d ...	2011	21380812
central nervous system sites of the sleep promoting effects of eszopiclone in rats.	we examined the effects of eszopiclone (esz), a gaba-a receptor agonist in current clinical use as a hypnotic medication, on the activity of subcortical wake- and sleep-active neuronal populations in the rat brain. sleep-wake states were quantified after i.p. injections of esz (3 and 10 mg/kg) or vehicle administered early in the dark phase, when rats are spontaneously awake. rats were euthanized 2 h post-injection and brain tissue was processed for c-fos protein immunoreactivity (ir) and for ne ...	2011	21382446
infusion of modafinil into anterior hypothalamus or pedunculopontine tegmental nucleus at different time-points enhances waking and blocks the expression of recovery sleep in rats after sleep deprivation.	clinical studies have indicated that the primary pharmacological activity of modafinil (mod) is inducing wakefulness; however, the brain targets that underlie its wake-promoting activity have not been described. in the present study, we show that mod injected into sleep-wake related brain areas promoted alertness. if administered (10, 20, or 30 ++g/1 ++l) into either anterior hypothalamus (ah) or pedunculopontine tegmental nucleus (pptg) at 08:00, 12:00 or 16:00 h, mod enhanced wakefulness where ...	2011	21385582
sleep-waking discharge profiles of median preoptic and surrounding neurons in mice.	the median preoptic nucleus (mnpo), part of the anteroventral third ventricular region, plays a key role in body fluid homeostasis and cardiovascular regulation. recently, a cluster of neurons showing sleep-related c-fos immunoreactivity was found in the rat mnpo, and a subsequent electrophysiological study found that nearly 76% of rat mnpo neurons exhibit increased discharge during sleep. in a recent single unit recording study in mice, we found that sleep-active neurons are not localized in an ...	2011	21396987
the role of adenosine in the regulation of sleep.	this paper presents an overview of the current knowledge about the role of adenosine in the sleep-wake regulation with a focus on adenosine in the central nervous system, regulation of adenosine levels, adenosine receptors, and manipulations of the adenosine system by the use of pharmacological and molecular biological tools. the endogenous somnogen prostaglandin (pg) d(2) increases the extracellular level of adenosine under the subarachnoid space of the basal forebrain and promotes physiologica ...	2011	21401496
role of ghrh in sleep and growth impairments induced by upper airway obstruction in rats.	upper airway obstruction (uao) can lead to abnormal growth hormone homeostasis and growth retardation by unclear mechanisms. we explored the effect of uao on hypothalamic growth hormone releasing hormone (ghrh), which has a role in both sleep and growth hormone regulation. the tracheae of 22-day-old rats were narrowed; uao and sham-operated animals were sacrificed 16 days post-surgery. to stimulate slow wave sleep and growth hormone secretion, rats were treated with ritanserin (5-ht2 receptor an ...	2011	21406516
biphasic effects of baicalin, an active constituent of scutellaria baicalensis georgi, in the spontaneous sleep-wake regulation.	baicalin is an active compound originating from the root of scutellaria baicalensis georgi, which has been used for anti-inflammation, anti-bacteria, anti-hypertension, anti-allergy and sedation since ancient china, though the neuronal mechanisms involved in the sedative effect is still unclear. baicalin possesses the ability to decrease the expression of pro-inflammatory cytokines and nuclear factor (nf)-?b activity. furthermore, baicalin has demonstrated an anxiolytic-like effect via activatio ...	2011	21419210
status epilepticus induces increasing neuronal excitability and hypersynchrony as revealed by optical imaging.	in the wake of acquired brain insults such as status epilepticus (se), time-dependent neuronal network alterations may occur resulting in cortical hyperexcitability and enhanced synchrony merging into chronic epilepsy. to better understand the underlying processes, we performed electrophysiological and optical imaging studies on combined hippocampal-entorhinal cortex slices. these were prepared from rats 1, 4 and 8 weeks after electrically-induced se. non-invasive imaging using intrinsic optical ...	2011	21440625
odor fear conditioning modifies piriform cortex local field potentials both during conditioning and during post-conditioning sleep.	sleep plays an active role in memory consolidation. sleep structure (rem/slow wave activity [sws]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. while the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rap ...	2011	21448432
serotonin control of sleep-wake behavior.	based on electrophysiological, neurochemical, genetic and neuropharmacological approaches, it is currently accepted that serotonin (5-ht) functions predominantly to promote wakefulness (w) and to inhibit rem (rapid eye movement) sleep (rems). yet, under certain circumstances the neurotransmitter contributes to the increase in sleep propensity. most of the serotonergic innervation of the cerebral cortex, amygdala, basal forebrain (bfb), thalamus, preoptic and hypothalamic areas, raphe nuclei, loc ...	2011	21459634
l-dopa activates histaminergic neurons.	l-dopa is the most effective treatment of early and advanced stages of parkinson's disease (pd), but its chronic use leads to loss of efficiency and dyskinesia. this is delayed by lower dosage at early stages, made possible by additional treatment with histamine antagonists. we present here evidence that histaminergic tuberomamillary nucleus (tmn) neurons, involved in the control of wakefulness, are excited under l-dopa (ec50 15 μm), express dopa decarboxylase and show dopamine immunoreactivity. ...	2011	21242252
effects on sleep and dopamine levels of microdialysis perfusion of cannabidiol into the lateral hypothalamus of rats.	the major non-psychoactive component of cannabis sativa, cannabidiol (cbd), displays a plethora of actions including wakefulness. in the present study, we addressed whether perfusing cbd via microdialysis into lateral hypothalamus (lh) during the lights-on period would modify the sleep-wake cycle of rats as well as the contents of dopamine (da) collected from nucleus accumbens (acbc). additionally, we tested whether perfusion of cbd into lh would block the sleep rebound after a sleep deprivation ...	2011	21262236
a new automated method for rat sleep deprivation with minimal confounding effects on corticosterone and locomotor activity.	the function of sleep in physiology, behaviour and cognition has become a primary focus of neuroscience. its study inevitably includes experimental sleep deprivation designs. however, concerns exist regarding confounds like stress, increased locomotor activity levels, and decreased motivation to perform operant tasks induced by the methods employed. we here propose a novel procedure for sleep deprivation in rats and evaluate how it affects sleep, corticosterone concentration profiles, locomotor ...	2011	21262261
nitric oxide production in the perifornical-lateral hypothalamic area and its influences on the modulation of perifornical-lateral hypothalamic area neurons.	the perifornical-lateral hypothalamic area (pf-lha) is a major wake-promoting structure. it predominantly contains neurons that are active during behavioral and cortical activation. pf-lha stimulation produces arousal and pf-lha lesions produce somnolence. nitric oxide (no) is a gaseous neurotransmitter that has been implicated in the regulation of multiple pathological and physiological processes including the regulation of sleep. no levels are higher in the cortex and in the basal forebrain (b ...	2011	21277356
evidence for cellular injury in the midbrain of rats following chronic constriction injury of the sciatic nerve.	complex behavioural disabilities, as well as pain, characterise neuropathic pain conditions for which clinical treatment is sought. in rats, chronic constriction injury (cci) of the sciatic nerve evokes, allodynia and hyperalgesia as well as three distinct patterns of disability, characterised by changes in social and sleep-wake behaviours: (i) pain & disability; (ii) pain & transient disability and (iii) pain alone. importantly, the degree of allodynia and hyperalgesia is identical for each of ...	2011	21291996
neuromedin u(2) receptor signaling mediates alteration of sleep-wake architecture in rats.	growing evidence indicates that neuromedin u (nmu) neuropeptide system plays an integral role in mediating the stress response through the corticotrophin-releasing factor (crf) pathways. stress is often associated with alteration in sleep-wake architecture both in human and laboratory animals. here, we investigated whether activation of the nmu2 receptor, a major high affinity receptor for nmu predominantly expressed in the brain, affects sleep behavior in rats. effects of single (acute) intrace ...	2011	21296417
characterization of pharmacological and wake-promoting properties of the dopaminergic stimulant sydnocarb in rats.	sydnocarb is a psychomotor stimulant structurally similar to d-amphetamine (d-amph) and is used in russia for the treatment of a variety of neuropsychiatric comorbidities. the nature of sydnocarb-induced facilitation of dopamine (da) neurotransmission [da release versus da transporter (dat) inhibition] is not clear. the present study characterized the pharmacological actions and behavioral effects of intraperitoneal sydnocarb in male sprague-dawley rats. where relevant, comparisons were made wit ...	2011	21300706
functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists.	orexins are neuro-modulatory peptides involved in the control of diverse physiological functions through interaction with two receptors, orexin-1 (ox1r) and orexin-2 (ox2r). recent evidence in pre-clinical models points toward a putative dichotomic role of the two receptors, with ox2r predominantly involved in the regulation of the sleep/wake cycle and arousal, and the ox1r being more specifically involved in reward processing and motivated behaviour. however, the specific neural substrates unde ...	2011	21307957
the influence of autonomic interventions on the sleep-wake-related changes in gastric myoelectrical activity in rats.	significant changes in autonomic activity occur at sleep-wake transitions and constitute an ideal setting for investigating the modulatory role of the autonomic nervous system on gastric myoelectrical activity (gma).	2011	21342364
ghrelin in mental health, sleep, memory.	ghrelin acts as a neuropeptide. it participates in sleep-wake regulation. after systemic ghrelin treatment nonrem sleep is promoted in male humans and mice. this effect is influenced by gender, time of administration and depression. ghrelin does not modulate sleep in healthy women and during the early morning in male subjects. in depressed women rem sleep is diminished after ghrelin. in elderly men and depressed men sleep promotion by ghrelin was preserved. in rats after central ghrelin feeding ...	2011	21349316
metabolic fingerprint of ischaemic cardioprotection: importance of the malate-aspartate shuttle.	the convergence of cardioprotective intracellular signalling pathways to modulate mitochondrial function as an end-target of cytoprotective stimuli is well described. however, our understanding of whether the complementary changes in mitochondrial energy metabolism are secondary responses or inherent mechanisms of ischaemic cardioprotection remains incomplete. in the heart, the malate-aspartate shuttle (mas) constitutes the primary metabolic pathway for transfer of reducing equivalents from the ...	2011	21349875
effects of the 5-ht₆ receptor antagonists sb-399885 and ro-4368554 and of the 5-ht(2a) receptor antagonist emd 281014 on sleep and wakefulness in the rat during both phases of the light-dark cycle.	the effects of the 5-ht₆ receptor antagonists sb-399885 (2.5, 5 and 10 mg/kg) and ro-4368554 (2.5, 5 and 10 mg/kg) and of the 5-ht(2a) receptor antagonist emd 281014 (2.5, 5 and 10 mg/kg) were studied in rats implanted for chronic sleep procedures. administration of 10 mg/kg sb-399885, i.p., to rats 2 h after the beginning of the light phase of the light-dark cycle caused a significant increase of wakefulness (w) and a reduction of slow wave sleep (sws), rem sleep (rems) and the number of rem pe ...	2011	20732355
ectopic overexpression of orexin alters sleep/wakefulness states and muscle tone regulation during rem sleep in mice.	orexins (also called hypocretins), which are neuropeptides exclusively expressed by a population of neurons specifically localized in the lateral hypothalamic area, are critically implicated in the regulation of sleep/wake states. orexin deficiency results in narcoleptic phenotype in rodents, dogs, and humans, suggesting that orexins are important for maintaining consolidated wakefulness states. however, the physiological effect of constitutive increased orexinergic transmission tone, which migh ...	2011	20711757
activation of extracellular signal-regulated kinase signaling in the pedunculopontine tegmental cells is involved in the maintenance of sleep in rats.	considerable evidence suggests that receptor-mediated excitation and inhibition of brainstem pedunculopontine tegmental (ppt) neurons are critically involved in the regulation of sleep-wake states. however, the molecular mechanisms operating within the ppt-controlling sleep-wake states remain relatively unknown. this study was designed to examine sleep-wake state-associated extracellular-signal-regulated kinase 1 and 2 (erk1/2) transduction changes in the ppt of freely moving rats. the results o ...	2011	21166678
dynamics of sleep-wake cyclicity across the fetal period in sheep (ovis aries).	all adult mammals examined thus far exhibit sleep bout durations that follow an exponential distribution and wake bout durations that follow a power-law distribution. in altricial rodents such as rats and mice, exponential distributions of sleep bouts are found soon after birth, but the power-law distribution of wake bouts does not emerge until the third postnatal week. also, both sleep and bouts consolidate across the early postnatal period. it is not known whether similar developmental process ...	2011	20886534
orexin-b-saporin lesions in the lateral hypothalamus enhance photic masking of rapid eye movement sleep in the albino rat.	the 24-h distribution of rapid eye movement (rem) sleep is known to be deeply reshaped among albino rats with neurotoxic lesions in the lateral hypothalamus (lh) or among rodent models of human narcolepsy-cataplexy, with selective damage of orexinergic neurones. we explored the hypothesis that this phenomenon is explained by an enhancement of rem sleep photic masking, as a consequence of damage in the lh. orexin-b-saporin neurotoxic lesions were induced in the lh of male sprague-dawley rats. lh- ...	2011	20626614
CEP-26401 (Irdabisant), a Potent and Selective Histamine H3 Receptor Antagonist/Inverse Agonist with Cognition-Enhancing and Wake-Promoting Activities.	CEP-26401 [irdabisant; 6-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-2H-pyridazin-3-one HCl] is a novel, potent histamine H(3) receptor (H(3)R) antagonist/inverse agonist with drug-like properties. High affinity of CEP-26401 for H(3)R was demonstrated in radioligand binding displacement assays in rat brain membranes (K(i) = 2.7 ± 0.3 nM) and recombinant rat and human H(3)R-expressing systems (K(i) = 7.2 ± 0.4 and 2.0 ± 1.0 nM, respectively). CEP-26401 displayed potent antagonist and in ...	2012	22001260
4,5-Dihydropyridazin-3-one derivatives as histamine H(3) receptor inverse agonists.	H(3)R structure-activity relationships for a new class of 4,5-dihydropyridazin-3-one H(3)R antagonists/inverse agonists are disclosed. Modification of the 4,5-dihydropyridazinone moiety to block in vivo metabolism identified 4,4-dimethyl-6-{4-[3-((R)-2-methyl-pyrrolidin-1-yl)-propoxy]-phenyl}-4,5-dihydro-2H-pyridazin-3-one 22 as a lead candidate demonstrating potent in vivo functional H(3)R antagonism in the rat dipsogenia model and robust wake promoting activity in the rat EEG/EMG model.	2012	22142542
estradiol treatment modulates spontaneous sleep and recovery after sleep deprivation in castrated male rats.	exogenous estradiol (e) is used occasionally to treat the side effects associated with androgen-deprivation in men, but its effects on sleep patterns have received little attention. we examined whether e modulates sleep patterns and recovery from sleep loss in castrated male rats. adult male rats were castrated and implanted subcutaneously with silastic tubes containing either oil (cast+oil) or e (cast+e). sham-operated male rats (intact) were implanted with oil-filled tubes. all rats were also ...	2012	22004978
Acute administration of fluoxetine normalizes rapid eye movement sleep abnormality, but not depressive behaviors in olfactory bulbectomized rats.	J. Neurochem. (2012) 120, 314-324. ABSTRACT: In humans, depression is associated with altered rapid eye movement (REM) sleep. However, the exact nature of the relationship between depressive behaviors and sleep abnormalities is debated. In this study, bilateral olfactory bulbectomy (OBX) was carried out to create a model of depression in rats. The sleep-wake profiles were assayed using a cutting-edge sleep bioassay system, and depressive behaviors were evaluated by open field and forced swimming ...	2012	22035172
role of the lateral paragigantocellular nucleus in the network of paradoxical (rem) sleep: an electrophysiological and anatomical study in the rat.	the lateral paragigantocellular nucleus (lpgi) is located in the ventrolateral medulla and is known as a sympathoexcitatory area involved in the control of blood pressure. in recent experiments, we showed that the lpgi contains a large number of neurons activated during ps hypersomnia following a selective deprivation. among these neurons, more than two-thirds are gabaergic and more than one fourth send efferent fibers to the wake-active locus coeruleus nucleus. to get more insight into the role ...	2012	22235249
midline thalamic paraventricular nucleus neurons display diurnal variation in resting membrane potentials, conductances and firing patterns in vitro.	neurons in the rodent midline thalamic paraventricular nucleus (pvt) receive inputs from brainstem and hypothalamic sites known to participate in sleep-wake and circadian rhythms. to evaluate possible diurnal changes in their excitability we used patch-clamp techniques to record and examine the properties of neurons in anterior pvt (apvt) in coronal rat brain slices prepared at zt 2-6 versus zt 14-18 and recorded at zt 8.4±0.2 (day) versus zt 21.2±0.2 (night), the subjective quiet versus aroused ...	2012	22219029