Intraventricular administration of neuropeptide S has reward-like effects.

doi:10.1016/J.EJPHAR.2011.02.009

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Intraventricular administration of neuropeptide S has reward-like effects.

Journal Article•DOI•

Intraventricular administration of neuropeptide S has reward-like effects.

Junran Cao¹, Luis de Lecea², Satoshi Ikemoto¹•Institutions (2)

United States Department of Health and Human Services¹, Stanford University²

01 May 2011-European Journal of Pharmacology (NIH Public Access)-Vol. 658, Iss: 1, pp 16-21

TL;DR: The data suggest that intraventricular NPS injections have reward-like effects in that NPS weakly facilitates seeking and induces positive reinforcement, which may depend on intact dopamine and hypocretin systems.

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About: This article is published in European Journal of Pharmacology.The article was published on 2011-05-01 and is currently open access. It has received 23 citations till now. The article focuses on the topics: Neuropeptide S & SCH-23390.

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Journal Article•DOI•

Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons.

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Csaba Adori¹, Swapnali Barde¹, Nenad Bogdanovic², Mathias Uhlén³, Rainer R. Reinscheid⁴, Gabor G. Kovacs⁵, Tomas Hökfelt¹ - Show less +3 more•Institutions (5)

Karolinska Institutet¹, University of Oslo², Royal Institute of Technology³, University of California, Irvine⁴, Medical University of Vienna⁵

25 Sep 2015-Frontiers in Neuroanatomy

TL;DR: The results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior, which must be considered when looking for targets for new pharmacotherapeutical interventions.

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Abstract: Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal-promoting effects of NPS make the NPS-NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 ± 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.

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29 citations

Cites background from "Intraventricular administration of ..."

...Recently, the pivotal role of glutamatergic projections from the ELPB nucleus, as a relay for arousal signal to the forebrain in obstructive sleep apnea syndrome (OSAS), was described (Chamberlin, 2013; Yokota et al., 2015)....
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Journal Article•DOI•

Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats.

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Christopher D. Schmoutz¹, Yanan Zhang², Scott P. Runyon², Nicholas E. Goeders¹•Institutions (2)

Louisiana State University¹, Research Triangle Park²

01 Dec 2012-Pharmacology, Biochemistry and Behavior

TL;DR: A small-molecule NPSR antagonist (RTI-118) was developed and tested and supported the hypothesis that antagonism of the neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and relapse.

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Abstract: Neuropeptide S (NPS) is a neuromodulatory peptide, acting via a G-protein-coupled receptor to regulate sleep, anxiety and behavioral arousal. Recent research has found that intracerebroventricular NPS can increase cocaine and alcohol self-administration in rodents, suggesting a key role in reward-related neurocircuitry. It is hypothesized that antagonism of the NPS system might represent a novel strategy for the pharmacological treatment of cocaine abuse. To this end, a small-molecule NPSR antagonist (RTI-118) was developed and tested in animal models of cocaine seeking and cocaine taking. Male Wistar rats (n=54) trained to self-administer cocaine and food under a concurrent alternating FR4 schedule exhibited specific dose-dependent decreases in cocaine intake when administered RTI-118. RTI-118 also decreased the reinstatement of extinguished cocaine-seeking behavior induced by conditioned cues, yohimbine and a priming dose of cocaine. These data support the hypothesis that antagonism of the neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and relapse.

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25 citations

Cites background from "Intraventricular administration of ..."

...The NPS system has also been implicated in addiction-related behaviors such as the modulation of subjective behavioral responses pertaining to reward and aversion (Cao et al., 2011)....
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...addiction-related behaviors such as the modulation of subjective behavioral responses pertaining to reward and aversion (Cao et al., 2011)....
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...Cao et al. (2011) found that ICV infusions of NPS modulate responses in a conditioned approach-avoidance paradigm....
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Journal Article•DOI•

Chronic ethanol potentiates the effect of neuropeptide s in the basolateral amygdala and shows increased anxiolytic and anti-depressive effects.

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Johan Enquist, Madeline Ferwerda, Anuradha Madhavan, Derek Hok, Jennifer L. Whistler¹ - Show less +1 more•Institutions (1)

University of California, San Francisco¹

27 Jun 2012-Neuropsychopharmacology

TL;DR: It is found that the anxiolytic and anti-depressant effects of NPS are enhanced in acute ethanol abstinent mice, and the NPSR may prove a suitable target for reducing relapse in alcoholism.

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22 citations

Cites background from "Intraventricular administration of ..."

...In contrast, Cao et al (2011) recently showed that NPS administration in rats can lead to both aversion and preference depending on which dose of NPS is used....
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Dissertation•

Neuropeptide S and mental health: A functional receptor gene variant and environment shaping traits and contributing to psychiatric disorders

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Kariina Laas

26 May 2014

Abstract: Hiljutiavastatud neuropeptiid S (NPS) avaldab narilistel omaparast moju, suurendades aktiivsust ja virgust samaaegselt arevuse alandamisega. Inimesel on NPS retseptori geenis NPSR1 funktsionaalne A>T polumorfism (rs324981), mille T-alleeli kooditud retseptorvalk on signaali vahendamisel tohusam. T-alleeli kandlus on seotud suurema virguse, kuid ka paanikahairega, mistottu on T-alleeli hakatud pidama riskialleeliks. Vaitekirjas kajastatud rahvastikupohiste uuringutega loime tasakaalustatuma pildi NPSR1 toimimisest, leides nii soost kui keskkonnast soltuvaid seoseid. Leidsime, et naistel, kellel on madalaima aktiivsusega NPSR1 genotuup, AA, voib juba teismeeas meeleolu ja arevuse regulatsiooniga raskusi olla. Mitteadaptiivsed jooned ilmnesid neil sagedamini just kehvade peresuhete korral, nagu ka suitsiidikatsed 18-ndaks ning arevus- ning meeleoluhaired 25-ndaks eluaastaks. Sagedamini kujunes A-alleeliga naistel valja ka alkoholisoltuvushaire. Seevastu meestel oli NPSR1 T-alleel, eriti TT genotuup, seotud huperaktiivsuse ja impulsiivsusega, ning stressirikkad elusundmused tostsid neid omadusi veelgi rohkem esile. Seetottu pole ullatav, et T-alleeliga meeste hulgas oli oluliselt rohkem soltuvushaireid. Huvitaval kombel raporteerisid sarnaselt naistega alkoholiga liialdamist taiskasvanuna hoopis AA genotuubiga mehed, mis viitab voimalikule taiendavale hilise algusega soltuvuse tekkimise rajale: AA meestel tousid adaptiivne impulsiivsus ja avatus oluliselt 25-ndaks eluaastaks, ning nad olid ka alkoholi kuritarvitamisele vastuvotlikumad. Kas neil ka hiljem soltuvus kujuneb, jaab tuleviku uuringute selgitada. NPSR on huvipakkuv sihtmark ravimiarenduseks, kuna mojutab virgust, emotsionaalseid reaktsioone ja alkoholi kuritarvitamist. AA ja TThomosugootide erinevaid emotsioonide reguleerimise viise on vaja sugavuti tundma oppida.; In this dissertation, we have focused on the functional rs324981 A>T polymorphism of the gene NPSR1 (Asn107Ile) that encodes for the neuropeptide S (NPS) receptor and is a relatively newly identified research target. We have shown that NPSR1 is associated with the development of personality, hyperactivity, anxiety, depressiveness, self-esteem, suicidality, affective/anxiety disorders, alcohol use and alcohol use disorders, and sleep-related measures. We have also found profound NPSR1 genotype by sex interactions in general population. In females, the probable lower NPS-ergic activity in the NPSR1 A-allele carriers, and especially in AA-homozygotes, bears a risk for affective and anxiety-related dysregulation already in adolescence. The risk for developing maladaptive traits is significantly higher in case of adverse family environment. As a consequence, females with the AA genotype had reported suicidal behaviour more frequently and had more often developed affective/anxiety disorders by age 25. Emotion dysregulation may also render them vulnerable to alcohol use, as some females carrying the A-allele develop AUD already in young adulthood. In males, an impulsivity-related early-onset pathway to…

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21 citations

Cites background from "Intraventricular administration of ..."

...In more detail, administration of NPS facilitated reward seeking and induced positive reinforcement (Cao et al. 2011), and reinstated cocaine (Paneda et al. 2009) and 19 alcohol seeking in rodents (Cannella et al. 2009a)....
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...…of the association is equivocal because in some experiments, higher NPS-ergic activity is related to substance seeking (Cannella et al. 2009a; Cao et al. 2011; Paneda et al. 2009), and in others it appears as protective against substance use and dependence (Badia-Elder et al. 2008; Enquist…...
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Journal Article•DOI•

Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice

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Julia J. Didonet¹, Judney Cley Cavalcante¹, Lisiane S. Souza¹, Miriam Stela Maris de Oliveira Costa¹, Eunice André², Vanessa de Paula Soares-Rachetti¹, Remo Guerrini³, Girolamo Calo³, Elaine C. Gavioli¹ - Show less +5 more•Institutions (3)

Federal University of Rio Grande do Norte¹, Federal University of Paraná², University of Ferrara³

01 Jun 2014-Behavioural Brain Research

TL;DR: NPS attenuated 6-OHDA-induced motor impairments in mice assessed in the rota-rod test and candidate NPSR agonists as a potential innovative treatment for PD are identified.

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21 citations

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References

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Journal Article•DOI•

Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity

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Peter W. Kalivas¹, Jane Stewart²•Institutions (2)

Washington State University¹, Concordia University²

01 Sep 1991-Brain Research Reviews

TL;DR: It is found that the dopamine neurons of sensitized animals have become increasingly sensitive to excitatory pharmacological and environmental stimuli or desensitized to inhibitory regulation, and changes in cellular activity or protein synthesis may result in a change in the presynaptic regulation of axon terminal dopamine release.

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2,042 citations

"Intraventricular administration of ..." refers background in this paper

..., 2005), while behavioral sensitization depends on their actions in the ventral tegmental area (Kalivas and Stewart, 1991; Kalivas and Weber, 1988; Vezina and Stewart, 1990)....
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Journal Article•DOI•

Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

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Satoshi Ikemoto¹•Institutions (1)

United States Department of Health and Human Services¹

01 Nov 2007-Brain Research Reviews

TL;DR: Experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the vents of the ventral striatum.

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1,387 citations

"Intraventricular administration of ..." refers background in this paper

...Because dopamine transmission occurring in the medial part of the ventral striatum plays a critical role in reward seeking (Ikemoto, 2007; Shin et al., 2010), the medial ventral striatum may play a critical role in cue-assisted self-administration of NPS....
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Journal Article•DOI•

Neuropeptide S: A Neuropeptide Promoting Arousal and Anxiolytic-like Effects

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Yan Ling Xu¹, Rainer K. Reinscheid¹, Salvador Huitron-Resendiz², Stewart D. Clark¹, Zhiwei Wang¹, Steven H.S. Lin¹, Fernando A. Brucher¹, Joanne Zeng¹, Nga Kim Ly¹, Steven J. Henriksen², Luis de Lecea², Olivier Civelli¹ - Show less +8 more•Institutions (2)

University of California, Irvine¹, Scripps Research Institute²

19 Aug 2004-Neuron

TL;DR: It is reported that a neuropeptide, NPS, potently modulates wakefulness and could also regulate anxiety, and it is shown that the LC region encompasses distinct nuclei expressing different arousal-promoting neurotransmitters.

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474 citations

"Intraventricular administration of ..." refers background in this paper

...In addition, the fact that intraventricular NPS promotes locomotor activity and wakefulness (Xu et al., 2004) makes it unclear whether increased lever pressing was due to enhanced seeking or “general” arousal....
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...Neuropeptide S (NPS) is a recently identified endogenous ligand of an orphan G protein coupled receptor (Xu et al., 2004)....
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Journal Article•DOI•

The hypocretins: setting the arousal threshold.

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J. Gregor Sutcliffe¹, Luis de Lecea¹•Institutions (1)

Scripps Research Institute¹

01 May 2002-Nature Reviews Neuroscience

TL;DR: Over a short period in the late 1990s, three groups converged on the discovery of a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates arousal states, influences feeding and is implicated in the sleep disorder narcolepsy.

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Abstract: Over a short period in the late 1990s, three groups converged on the discovery of a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates arousal states, influences feeding and is implicated in the sleep disorder narcolepsy. Subsequent studies have illuminated many aspects of the circuitry of the hypocretin (also called orexin) system, which also influences hormone secretion and autonomic homeostasis, and have led to the hypothesis that most human narcolepsies result from an autoimmune attack against the hypocretin-producing neurons. The biochemical, physiological and anatomical components that regulate the switch between waking and sleeping are becoming clear. The rapidity with which the hypocretin story has emerged is a testament to both the conceptual and the technical evolution of genomic science in the past two decades.

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426 citations

Journal Article•DOI•

Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory.

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Satoshi Ikemoto¹•Institutions (1)

United States Department of Health and Human Services¹

01 Nov 2010-Neuroscience & Biobehavioral Reviews

TL;DR: A neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach is outlined.

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391 citations

"Intraventricular administration of ..." refers background in this paper

...…to be expressed throughout the brain (Leonard and Ring, 2011; Xu et al., 2007), including in the regions that are associated with reward processes (Ikemoto, 2010): the ventral tegmental area, olfactory tubercle, bed nucleus of stria terminalis, diagonal band, paraventricular thalamic nucleus,…...
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..., 2007), including in the regions that are associated with reward processes (Ikemoto, 2010): the ventral tegmental area, olfactory tubercle, bed nucleus of stria terminalis, diagonal band, paraventricular thalamic nucleus, preoptic area, lateral and posterior hypothalamic areas, periaqueductal gray, median and dorsal raphe nuclei and parabrachial nucleus....
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