Assessment of the Neuropeptide S System in Anxiety Disorders

Donner, Jonas; Haapakoski, Rita; Ezer, Sini; Melén, Erik; Pirkola, Sami; Gratacòs, Mónica; Zucchelli, Marco; Anedda, Francesca; Johansson, Lars-Åke; Söderhäll, Cilla; Orsmark-Pietras, Christina; Suvisaari, Jaana; Martín‐Santos, Rocío; Torrens, Marta; Silander, Kaisa; Terwilliger, Joseph D.; Wickman, Magnus; Pershagen, Göran; Lönnqvist, Jouko; Peltonen, Leena; Estivill, Xavier; D’Amato, Mauro; Kere, Juha; Alenius, Harri; Hovatta, Iiris

doi:10.1016/j.biopsych.2010.05.039

Cited by 79 publications

(67 citation statements)

References 49 publications

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“…Within this theme it is interesting to note that neuropeptide (NPS), a neuropeptidergic transmitter acting via G protein-coupled receptors (NPS-Rs) to modulate anxiety and arousal (Xu et al, 2004;Jüngling et al, 2008;, increases responsiveness of intercalated GABAergic neurons in the murine amygdala and thereby facilitates fear extinction learning and recall (Jüngling et al, 2008). Furthermore, a functional polymorphism in the NPS-R gene (rs324981 A/T) has been associated with overinterpretation of learned fear and panic disorders in humans and is associated with increased amygdala responsiveness to fear-relevant stimuli (Raczka et al, 2010;Dannlowski et al, 2011;Domschke et al, 2011;Donner et al, 2010). Of particular interest, here is that forced swim stress results in increased c-fos activity in NPS-synthesizing neurons in the brain stem (Liu et al, 2011) and increase extracellular levels of NPS in the BLA (Ebner et al, 2011), implying that the NPS system may be stimulated on stress exposure.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Stress-Impaired Fear Extinction Through Neuropeptide S Action in the Lateral Amygdala

Chauveau

Lange

Jüngling

et al. 2012

Neuropsychopharmacol

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Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety-like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to preconditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction.

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Section: Introductionmentioning

confidence: 99%

Prevention of Stress-Impaired Fear Extinction Through Neuropeptide S Action in the Lateral Amygdala

Chauveau

Lange

Jüngling

et al. 2012

Neuropsychopharmacol

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“…However, in carriers of the more active NPSR TT genotype -previously found to be associated with anxiety and panic disorder Donner et al 2010;Okamura et al 2007) -administration of caffeine synergistically resulted in an increased startle magnitude in the neutral emotional condition. After presentation of unpleasant emotional stimuli, however, NPSR TT genotype carriers showed a blunted startle magnitude in response to caffeine.…”

Section: Discussionmentioning

confidence: 93%

“…In rodent models, NPS or neuropeptide S receptor (NPSR) agonists reliably elicit anxiolytic effects, paralleled by a robustly increased arousal as expressed by elevated locomotor activity and increased wakefulness (Leonard et al 2008;Rizzi et al 2008;Wegener et al 2011;Xu et al 2004; for review, see Pape et al 2010;), while NPSR knock-out mice exhibit increased anxiety-like behavior and accordingly reduced behavioral arousal as mirrored by decreased exploratory activity along with an increase in rest time (Duangdao et al 2009). In humans, contrary to most animal data proposing an anxiolytic effect of NPS, the more active T allele of the functional A/T (Asn 107 Ile; rs324981) variant in the NPSR has consistently been reported to be associated with panic disorder in several independent samples Donner et al 2010;Okamura et al 2007). Furthermore, NPSR T allele carriers showed significantly elevated anxiety sensitivity and increased autonomic arousal during a behavioral avoidance test ).…”

Section: Introductionmentioning

confidence: 95%

Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation

et al. 2012

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“…Recent and numerous data indicate that pharmacological modulation of NPS may be a potential way to treat these comorbid disorders. The anxiolytic-like effect of NPS has been established in a number of preclinical models [10,34,35], whereas the antidepressant potential of NPS has revealed conflicting results. Accordingly, earlier reports do not support the involvement of the NPS neuronal circuitry in the regulation of depression-related behaviour [10], whereas recent findings demonstrated that NPS exerted an antidepressant-like activity in a genetic animal model of depression i.e.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide-S Evoked Arousal with Electroencephalogram Slow-Wave Compensatory Drive in Rats

Ahnaou¹,

Drinkenburg²

2012

Neuropsychobiology

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Objectives: Neuropeptide S (NPS) exerts a dual arousal and anxiolytic effect in rodents, which may indicate the potential of a novel class of therapeutic agents in psychiatry. The purpose of this study is to fully describe the nature of electroencephalogram (EEG)-defined waking that mediates these arousal effects. Methods: Effects of the intracerebroventricular infusion of NPS at 2 different doses were characterized over 20 h on sleep-wake architecture and EEG spectral components in rats that were chronically implanted with epidural electrodes for continuous measurement of sleep polygraphic and EEG variables. Results: NPS (1 and 10 nmol) increased active waking (+88 and +87%, respectively), decreased light slow-wave sleep (lSWS) (–84 and –68%, respectively), deep slow-wave sleep (dSWS) (–47 and –33%, respectively) and rapid-eye-movement sleep (–71 and –70%, respectively) during the first 2 h after infusion. The wake-promoting effect of NPS is consistent with a marked lengthening in latency to sleep onset, a decrease in the number of state transitions from wakefulness to lSWS, and a delayed lSWS compensatory response. Interestingly, NPS significantly enhanced waking EEG theta oscillations and slow wave activity during dSWS. Conclusion: The findings suggest that NPS enhanced a consolidated waking associated with a subsequent compensatory EEG slow-wave homeostatic drive rather than rebound sleep duration. The characteristics of NPS-induced waking coupled with enhanced EEG theta oscillations without rebound in sleep are desirable therapeutic features in wake-promoting agents.

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Assessment of the Neuropeptide S System in Anxiety Disorders

Cited by 79 publications

References 49 publications

Prevention of Stress-Impaired Fear Extinction Through Neuropeptide S Action in the Lateral Amygdala

Prevention of Stress-Impaired Fear Extinction Through Neuropeptide S Action in the Lateral Amygdala

Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation

Neuropeptide-S Evoked Arousal with Electroencephalogram Slow-Wave Compensatory Drive in Rats

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