| 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 |
| melatonin receptor agonists: new options for insomnia and depression treatment. | the circadian nature of melatonin (mlt) secretion, coupled with the localization of mlt receptors to the suprachiasmatic nucleus, has led to numerous studies of the role of mlt in modulation of the sleep-wake cycle and circadian rhythms in humans. although much more needs to be understood about the various functions exerted by mlt and its mechanisms of action, three therapeutic agents (ramelteon, prolonged-release mlt, and agomelatine) are already in use, and mlt receptor agonists are now appear ... | 2010 | 21554566 |
| 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 |
| methods for neural ensemble recordings | electrical activity is essential for neuronal communication. over the years, in vivo multielectrode recordings have revealed that the electrical activities of individual neurons are not independent of each other. instead, neurons tend to fire in a coordinated way within a given neural network. when measured as the electroencephalogram (eeg) or local field potential (lfp) signals, this neural coordination results in complex oscillatory activity patterns, which reflect synchronous synaptic potenti ... | 2008 | 21204450 |
| [advances in the study of histaminergic systems and sleep-wake regulation]. | histaminergic neurons solely originate from the tuberomammillary nucleus (tmn) in the posterior hypothalamus and send widespread projections to the whole brain. experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes. endogeneous prostaglandin e2 and orexin activate histaminergic neurons in the tmn to release histamine and promote wakefulnes ... | 2011 | 21626776 |
| maternal stress induces adult reduced rem sleep and melatonin level. | objectives: we have previously reported that neonatal maternal deprivation (md) resulted in a decrease of total sleep and an increase of orexin a in adult rats. now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with md and control (mc) procedures. design: adult male sprague dawley rats were treated with either md or mc procedures for ten days starting at postnatal day 4. at three months of age, sleep was recorded for 48 hours in one set of md and ... | 2011 | 21805687 |
| norepinephrine infusion into nucleus basalis elicits microarousal in desflurane-anesthetized rats. | background:: the nucleus basalis of meynert of the basal forebrain has been implicated in the regulation of the state of consciousness across normal sleep-wake cycles. its role in the modulation of general anesthesia was investigated. methods:: rats were chronically implanted with bilateral infusion cannulae in the nucleus basalis of meynert and epidural electrodes to record the electroencephalogram in frontal and visual cortices. animals were anesthetized with desflurane at a concentration requ ... | 2011 | 21804378 |
| identification of pyridazin-3-one derivatives as potent, selective histamine h(3) receptor inverse agonists with robust wake activity. | h(3)r structure-activity relationships on a novel class of pyridazin-3-one h(3)r antagonists/inverse agonists are disclosed. modifications of the pyridazinone core, central phenyl ring and linker led to the identification of molecules with excellent target potency, selectivity and pharmacokinetic properties. compounds 13 and 21 displayed potent functional h(3)r antagonism in vivo in the rat dipsogenia model and demonstrated robust wake activity in the rat eeg/emg model. | 2011 | 21782432 |
| administration of urb597, oleoylethanolamide or palmitoylethanolamide increases waking and dopamine in rats. | oleoylethanolamide (oea) and palmitoylethanolamide (pea) are amides of fatty acids and ethanolamine named n-acylethanolamines or acylethanolamides. the hydrolysis of oea and pea is catalyzed by the fatty acid amide hydrolase (faah). a number of faah inhibitors that increase the levels of oea and pea in the brain have been developed, including urb597. in the present report, we examined whether urb597, oea or pea injected into wake-related brain areas, such as lateral hypothalamus (lh) or dorsal r ... | 2011 | 21779318 |
| inhibition of hippocampal neurogenesis by sleep deprivation is independent of circadian disruption and melatonin suppression. | procedures that restrict or fragment sleep can inhibit neurogenesis in the hippocampus of adult rodents, although the underlying mechanism is unknown. we showed that rapid-eye-movement (rem) sleep deprivation (rsd) by the platform-over-water method inhibits hippocampal cell proliferation in adrenalectomized rats with low-dose corticosterone clamp. this procedure also greatly disrupts daily behavioral rhythms. given recent evidence for circadian clock regulation of cell proliferation, we asked wh ... | 2011 | 21771640 |
| ghrelin postsynaptically depolarizes dorsal raphe neurons in rats in vitro. | ghrelin promotes growth hormone (gh) secretion and feeding. recent studies further showed that ghrelin displayed a defending effect against the depressive-like symptoms and affected sleep in animals and humans. serotonergic system is considered to be implicated in feeding, depression and other mood disorders, and sleep. the dorsal raphe nucleus (drn) utilizes serotonin (5-ht) as its major neurotransmitter and expresses gh secretagogue receptors (ghs-rs). therefore, the present study was carried ... | 2011 | 21763741 |
| enac structure and function in the wake of a resolved structure of a family member. | our understanding of epithelial na(+) channel (enac) structure and function has been profoundly impacted by the resolved structure of the homologous acid sensing ion channel 1 (asic1). the structure of the extracellular and pore regions provide insight into channel assembly, processing, and the ability of these channels to sense the external environment. the absence of intracellular structures precludes insight into important interactions with intracellular factors that regulate trafficking and ... | 2011 | 21753073 |
| the kca3.1 blocker tram-34 reduces infarction and neurological deficit in a rat model of ischemia/reperfusion stroke. | microglia and brain infiltrating macrophages significantly contribute to the secondary inflammatory damage in the wake of ischemic stroke. here, we investigated whether inhibition of kca3.1 (ikca1/kcnn4), a calcium-activated k(+) channel that is involved in microglia and macrophage activation and expression of which increases on microglia in the infarcted area, has beneficial effects in a rat model of ischemic stroke. using an hplc/ms assay, we first confirmed that our small molecule kca3.1 bloc ... | 2011 | 21750563 |
| estradiol suppresses recovery of rem sleep following sleep deprivation in ovariectomized female rats. | sleep complaints such as insufficient sleep and insomnia are twice as prevalent in women. symptoms of sleep disruption are often coincident with changes in the gonadal hormone profile across a women's lifespan. data from a number of different species, including humans, non-human primates and rodents strongly implicate a role for gonadal hormones in the modulation of sleep. in female rats, increased levels of circulating estradiol increase wakefulness and reduce sleep in the dark phase. in this s ... | 2011 | 21722658 |
| association between the activation of mch and orexin immunorective neurons and rem sleep architecture during rem rebound after a three day long rem deprivation. | rapid eye movement (rem) sleep rebound following rem deprivation using the platform-on-water method is characterized by increased time spent in rem sleep and activation of melanin-concentrating hormone (mch) expressing neurons. orexinergic neurons discharge reciprocally to mch-ergic neurons across the sleep-wake cycle. however, the relation between rem architecture and the aforementioned neuropeptides remained unclear. mch-ergic neurons can be divided into two subpopulations regarding their coca ... | 2011 | 21740944 |
| diltiazem potentiates pentobarbital-induced hypnosis via 5-ht(1a) and 5-ht(2a/2c) receptors: role for dorsal raphe nucleus. | it has been reported that the sedative component of pentobarbital is mediated by gaba receptors in an endogenous sleep pathway and the ventrolateral preoptic area (vlpo)-tuberomammillary nucleus (tmn) or vlpo-dorsal raphe nucleus (drn) neural circuit is important in the sedative response to pentobarbital. our previous findings indicated that the vlpo-tmn neuronal circuit may play crucial part in the augmentative effect of diltiazem on pentobarbital sleep and the serotonergic system may be involv ... | 2011 | 21689675 |
| sleep duration varies as a function of glutamate and gaba in rat pontine reticular formation. | the oral part of the pontine reticular formation (pno) is a component of the ascending reticular activating system and plays a role in the regulation of sleep and wakefulness. the pno receives glutamatergic and gabaergic projections from many brain regions that regulate behavioral state. indirect, pharmacological evidence has suggested that glutamatergic and gabaergic signaling within the pno alters traits that characterize wakefulness and sleep. no previous studies have simultaneously measured ... | 2011 | 21679185 |
| chronic exposure to toluene changes the sleep-wake pattern and brain monoamine content in rats. | toluene, found in glues and cleaners, is among the inhalants most commonly abused by workers and young drug addicts. in this study, we examined the changes in sleep patterns and monoamine content induced by chronic toluene exposure. rats were chronically exposed to toluene vapors beginning at 30 days of age for a duration of 30 days. experiment i was performed in a control group (n=10) and a chronic toluene exposure group (n=10). rats were implanted with bipolar stainless steel electrodes for el ... | 2011 | 21731073 |
| opposite effects of cortisol on consolidation of temporal sequence memory during waking and sleep. | memory functions involve three stages: encoding, consolidation, and retrieval. modulating effects of glucocorticoids (gcs) have been consistently observed for declarative memory with gcs enhancing encoding and impairing retrieval, but surprisingly, little is known on how gcs affect memory consolidation. studies in rats suggest a beneficial effect of gcs that were administered during postlearning wake periods, whereas in humans, cortisol impaired memory consolidation when administered during post ... | 2011 | 21736452 |
| 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 |
| 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 |
| 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 |
| cellular and network mechanisms of genetically-determined absence seizures. | the absence epilepsies are characterized by recurrent episodes of loss of consciousness associated with generalized spike-and-wave discharges, with an abrupt onset and offset, in the thalamocortical system. in the absence of detailed neurophysiological studies in humans, many of the concepts regarding the pathophysiological basis of absence seizures are based on studies in animal models. each of these models has its particular strengths and limitations, and the validity of findings from these mo ... | 2007 | 21909233 |
| [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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| automated sleep scoring in rats and mice using the naive bayes classifier. | we describe a new simple matlab-based method for automated scoring of rat and mouse sleep using the naive bayes classifier. this method is highly sensitive resulting in overall auto-rater agreement of 93%, comparable to an inter-rater agreement between two human scorers (92%), with high sensitivity and specificity values for wake (94% and 96%), nrem sleep (94% and 97%) and rem sleep (89% and 97%) states. in addition to baseline sleep-wake conditions, the performance of the naive bayes classifier ... | 2011 | 21884727 |
| Quantitative differences among EMG activities of muscles innervated by subpopulations of hypoglossal and upper spinal motoneurons during non-REM sleep - REM sleep transitions: a window on neural processes in the sleeping brain. | In the rat, a species widely used to study the neural mechanisms of sleep and motor control, lingual electromyographic activity (EMG) is minimal during non-rapid eye movement (non-REM) sleep and then phasic twitches gradually increase after the onset of REM sleep. To better characterize the central neural processes underlying this pattern, we quantified EMG of muscles innervated by distinct subpopulations of hypoglossal motoneurons and nuchal (N) EMG during transitions from non-REM sleep to REM ... | 2011 | 22205596 |
| Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression. | Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil trea ... | 2011 | 22036079 |
| Evoked electrical and cerebral vascular responses during sleep and following sleep deprivation. | Neuronal activity elicits vascular dilation, delivering additional blood and metabolites to the activated region. With increasing neural activity, vessels stretch and may become less compliant. Most functional imaging studies assume that limits to vascular expansion are not normally reached except under pathological conditions, with the possibility that metabolism could outpace supply. However, we previously demonstrated that evoked hemodynamic responses were larger during quiet sleep when compa ... | 2011 | 21854966 |
| Calcium/calmodulin kinase II in the pedunculopontine tegmental nucleus modulates the initiation and maintenance of wakefulness. | The pedunculopontine tegmentum nucleus (PPT) is critically involved in the regulation of wakefulness (W) and rapid eye movement (REM) sleep, but our understanding of the mechanisms of this regulation remains incomplete. The present study was designed to determine the role of PPT intracellular calcium/calmodulin kinase (CaMKII) signaling in the regulation of W and sleep. To achieve this aim, three different concentrations (0.5, 1.0, and 2.0 nmol) of the CaMKII activation inhibitor, KN-93, were mi ... | 2011 | 22114270 |
| Sleep and wake in rhythmic versus arrhythmic chronotypes of a microphthalmic species of African mole rat (Fukomys mechowii). | The giant Zambian mole rat (Fukomys mechowii) is a subterranean Afrotropical rodent noted for its regressed visual system and unusual patterns of circadian rhythmicity--within this species some individuals exhibit distinct regular circadian patterns of locomotor activity while others have arrhythmic circadian patterns. The current study was aimed at understanding whether differences in circadian chronotypes in this species affect the patterns and proportions of the different phases of the sleep- ... | 2011 | 21952092 |
| Circadian regulation of sleep-wake behaviour in nocturnal rats requires multiple signals from suprachiasmatic nucleus. | The dynamics of sleep and wake are strongly linked to the circadian clock. Many models have accurately predicted behaviour resulting from dynamic interactions between these two systems without specifying physiological substrates for these interactions. By contrast, recent experimental work has identified much of the relevant physiology for circadian and sleep-wake regulation, but interaction dynamics are difficult to study experimentally. To bridge these approaches, we developed a neuronal popul ... | 2011 | 21893532 |
| electrophysiological correlates of sleep homeostasis in freely behaving rats. | the electrical activity of the brain does not only reflect the current level of arousal, ongoing behavior, or involvement in a specific task but is also influenced by what kind of activity, and how much sleep and waking occurred before. the best marker of sleep-wake history is the electroencephalogram (eeg) spectral power in slow frequencies (slow-wave activity, 0.5-4 hz, swa) during sleep, which is high after extended wakefulness and low after consolidated sleep. while sleep homeostasis has bee ... | 2011 | 21854953 |
| Promotion of Non-Rapid Eye Movement Sleep and Activation of Reticular Thalamic Neurons by a Novel MT2 Melatonin Receptor Ligand. | Melatonin activates two brain G-protein coupled receptors, MT(1) and MT(2), whose differential roles in the sleep-wake cycle remain to be defined. The novel MT(2) receptor partial agonist, N-{2-[(3-methoxyphenyl) phenylamino] ethyl} acetamide (UCM765), is here shown to selectively promote non-rapid eye movement sleep (NREMS) in rats and mice. The enhancement of NREMS by UCM765 is nullified by the pharmacological blockade or genetic deletion of MT(2) receptors. MT(2), but not MT(1), knock-out mic ... | 2011 | 22171046 |
| Dynamics of Circadian Thalamocortical Flow of Information during a Peripheral Neuropathic Pain Condition. | It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field ... | 2011 | 22007162 |
| 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 |
| modeling the temporal architecture of rat sleep-wake behavior. | the fine architecture of sleep-wake behavior shows a distinct dynamic structure with distributions of rat sleep and wake bout durations displaying qualitatively different profiles. wake bout durations follow a power-law relation whereas sleep bout durations are exponentially distributed. we show that a physiologically-based sleep-wake regulatory network model with an underlying deterministic structure governing neuronal interactions can generate realistic rat sleep-wake behavior as assessed by b ... | 2011 | 22255390 |