Effect of basal forebrain neuropeptide Y administration on sleep and spontaneous behavior in freely moving rats

Department of Physiology and Neurobiology, Eötvös Loránd University, Pázmány Péter Sétány 1/C, H-1117 Budapest, Hungary.
Brain Research Bulletin (Impact Factor: 2.72). 06/2007; 72(4-6):293-301. DOI: 10.1016/j.brainresbull.2007.01.006
Source: PubMed


Neuropeptide Y (NPY) is present both in local neurons as well as in fibers in the basal forebrain (BF), an area that plays an important role in the regulation of cortical activation. In our previous experiments in anaesthetized rats, significant EEG changes were found after NPY injections to BF. EEG delta power increased while power in theta, alpha, and beta range decreased. The aim of the present experiments was to determine whether NPY infusion to BF can modulate sleep and behavior in freely moving rats. In this study, microinjections were made into the BF. Saline was injected to the control side, while either saline or one of two doses of NPY (0.5 microl, 300-500 pmol) to the treated side. EEG as well as behavioral changes were recorded. Behavioral elements after the NPY injections changed in a characteristic fashion in time and three consecutive phases were defined. In phase I (half hour 2), activated behavioral items (moving, rearing, grooming) appeared frequently. In phase II (half hours 3 and 4) activity decreased, while motionless state increased. Reappearance of activity was seen in phase III (half hours 5 and 6). NPY injections caused sleep-wake changes. The three phases described for behavioral changes were also reflected in the sleep data. During phase I, lower NPY dose increased wakefulness and decreased deep sleep. Reduced behavioral activity seen in phase II was partially reflected in the sleep. In this phase, wakefulness tended to increase in the third half hour, while decreased in the 4th half hour. Deep sleep and total slow wave sleep non-significantly decreased in the third and increased in the 4th half hour. In most cases, wakefulness was elevated again during Phase III, while sleep decreased. Length of single sleep-wake epochs did not change after NPY injections. Our results suggest a role for NPY in the integration of sleep and behavioral stages via the BF.

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    • "Despite recent findings in genetically tractable invertebrate models, the understanding of mechanisms that regulate sleep homeostasis remains incomplete (Andretic et al., 2008; Cirelli, 2009; Sehgal and Mignot, 2011; Driver et al., 2013; Shi et al., 2014). NPY was implicated in the regulation of sleep in humans, rats, fruit flies, and nematodes (Antonijevic et al., 2000; Tóth et al., 2007; Dyzma et al., 2010; Van den Pol, 2012; Choi et al., 2013; He et al., 2013; Nagy et al., 2014). In C. elegans, the NPY receptor homolog NPR-1 affects a range of responses to external stimuli, as well as innate behaviors such as social feeding and quiescence (De Bono and Bargmann, 1998; De Bono et al., 2002; Davies et al., 2004; Chang et al., 2006; Macosko et al., 2009; McGrath et al., 2009; Choi et al., 2013; Nagy et al., 2014). "
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    ABSTRACT: Biological homeostasis invokes modulatory responses aimed at stabilizing internal conditions. Using tunable photo- and mechano-stimulation, we identified two distinct categories of homeostatic responses during the sleep-like state of Caenorhabditis elegans (lethargus). In the presence of weak or no stimuli, extended motion caused a subsequent extension of quiescence. The neuropeptide Y receptor homolog, NPR-1, and an inhibitory neuropeptide known to activate it, FLP-18, were required for this process. In the presence of strong stimuli, the correlations between motion and quiescence were disrupted for several minutes but homeostasis manifested as an overall elevation of the time spent in quiescence. This response to strong stimuli required the function of the DAF-16/FOXO transcription factor in neurons, but not that of NPR-1. Conversely, response to weak stimuli did not require the function of DAF-16/FOXO. These findings suggest that routine homeostatic stabilization of sleep may be distinct from homeostatic compensation following a strong disturbance. DOI:
    Full-text · Article · Dec 2014 · eLife Sciences
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    • "In humans, NPY enhances sleep by prolonging the sleep period and reducing sleep latency and wakefulness [13]. In contrast, NPY in rats increases wakefulness and decreases sleep [14]. These findings indicate that NPY regulates sleep differently in different animal species, probably due to their diurnal or nocturnal difference. "
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    ABSTRACT: Sleep is important for maintenance of normal physiology in animals. In mammals, neuropeptide Y (NPY), a homolog of Drosophila neuropeptide F (NPF), is involved in sleep regulation, with different effects in human and rat. However, the function of NPF on sleep in Drosophila melanogaster has not yet been described. In this study, we investigated the effects of NPF and its receptor-neuropeptide F receptor (NPFR1) on Drosophila sleep. Male flies over-expressing NPF or NPFR1 exhibited increased sleep during the nighttime. Further analysis demonstrated that sleep episode duration during nighttime was greatly increased and sleep latency was significantly reduced, indicating that NPF and NPFR1 promote sleep quality, and their action on sleep is not because of an impact of the NPF signal system on development. Moreover, the homeostatic regulation of flies after sleep deprivation was disrupted by altered NPF signaling, since sleep deprivation decreased transcription of NPF in control flies, and there were less sleep loss during sleep deprivation and less sleep gain after sleep deprivation in flies overexpressing NPF and NPFR1 than in control flies, suggesting that NPF system auto-regulation plays an important role in sleep homeostasis. However, these effects did not occur in females, suggesting a sex-dependent regulatory function in sleep for NPF and NPFR1. NPF in D1 brain neurons showed male-specific expression, providing the cellular locus for male-specific regulation of sleep by NPF and NPFR1. This study brings a new understanding into sleep studies of a sexually dimorphic regulatory mode in female and male flies.
    Full-text · Article · Sep 2013 · PLoS ONE
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    • "Many other peptides exhibit such a biphasic effect. For example, NPY also increases or decreases sleep depending on the dose employed (Tóth et al., 2007). Similar effects have been described for somatostatin , as this peptide increases or decreases food ingestion depending on the dose (Feifel and Vicarino, 1990). "
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    ABSTRACT: It is known that the sleep-waking cycle is modulated by several molecules that may also regulate food intake, among them several neuropeptides. The cocaine-and-amphetamine-regulated transcript has been studied in relation to food ingestion, but it seems to have several other functions that may include sleep regulation. In this context, we studied the effect of the intracerebroventricular administration of the cocaine-and-amphetamine-regulated transcript (0.15, 0.3, 0.6, 0.9nmol) on the sleep-waking cycle (12-h recordings), as well as its effect on food intake in rats. Additionally, we analyzed the neuronal activity as measured by c-Fos expression induced by the cocaine-and-amphetamine-regulated transcript in neurons of nuclei involved in the regulation of sleep and feeding behavior. Our main finding is that 0.3nmol of the cocaine-and-amphetamine-regulated transcript increases rapid-eye-movement sleep. In addition, our results further support that this neuropeptide triggers satiety; c-Fos expression suggested that the cocaine-and-amphetamine-regulated transcript activates specific hypothalamic nuclei without affecting other brain structures known to be involved in sleep regulation. These data further support the notion that a few neuropeptides are involved in the regulation of both the sleep-waking and the hunger-satiety cycles.
    Full-text · Article · Sep 2009 · Neuropeptides
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