Neuropeptide S receptor gene: Fear-specific modulations of prefrontal activation

Tupak, Sara V.; Reif, Andreas; Pauli, Paul; Dresler, Thomas; Herrmann, Martin J.; Domschke, Katharina; Jochum, Clara; Haas, Elisabeth A.; Baumann, Christian; Weber, Heike; Fallgatter, Andreas J.; Deckert, Jürgen; Ehlis, Ann‐Christine

doi:10.1016/j.neuroimage.2012.10.033

Cited by 30 publications

(21 citation statements)

References 62 publications

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“…Human, as well as rodent studies investigating the role of the NPS system in anxiety‐related behaviors have come to the general consensus that NPS plays an important role in the regulation of anxiety, fear and stress‐related behaviors . Generally, NPSR‐deficient animals show a more anxious phenotype but not impaired contextual or cued fear learning .…”

Section: Discussionmentioning

confidence: 99%

“…39,40 Human, as well as rodent studies investigating the role of the NPS system in anxiety-related behaviors have come to the general consensus that NPS plays an important role in the regulation of anxiety, fear and stress-related behaviors. [17][18][19][20][21] Generally, NPSR-deficient animals show a more anxious phenotype but not impaired contextual or cued fear learning. 39,41,42 Here we show that NPSR-deficiency leads to improved safety learning in mice which were not pre-exposed to electric stimuli, that is, NPSR-deficiency has beneficial effects in mice that have not encounter an aversive experience.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of research indicate that safety learning is impaired in patients suffering from anxiety disorders, such as panic disorder or post‐traumatic stress disorder . Interestingly, genetic studies in humans have found that several single‐nucleotide polymorphisms and splice variants of the human NPSR gene have been associated with higher incidences of anxiety disorders . Nevertheless, up until now, no human or rodent study investigated the role of the NPS system in safety learning.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15][16] Interestingly, genetic studies in humans have found that several single-nucleotide polymorphisms and splice variants of the human NPSR gene have been associated with higher incidences of anxiety disorders. [17][18][19][20][21] Nevertheless, up until now, no human or rodent study investigated the role of the NPS system in safety learning.…”

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confidence: 99%

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Neuropeptide‐S‐receptor deficiency affects sex‐specific modulation of safety learning by pre‐exposure to electric stimuli

Kreutzmann

Khalil

Köhler

et al. 2020

Genes Brain and Behavior

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Neuropeptide S (NPS) is a neuropeptide involved in the regulation of fear. Because safety learning is impaired in patients suffering from anxiety‐related psychiatric disorders, and polymorphisms of the human neuropeptide S receptor (NPSR) gene have also been associated with anxiety disorders, we wanted to investigate whether NPSR‐deficiency interferes with safety learning, and how prior stress would affect this type of learning. We first investigated the effect of pre‐exposure to two different types of stressors (electric stimuli or immobilization) on safety learning in female and male C57Bl/6 mice, and found that while stress induced by electric stimuli enhanced safety learning in males, there were no differences in safety learning following immobilization stress. To further investigate the role of the NPS system in stress‐induced modulation of safety learning, we exposed NPSR‐deficient mice to stress induced by electric stimuli 10 days before safety learning. In nonstressed male mice, NPSR‐deficiency enhanced safety learning. As in male C57Bl/6 mice, pre‐exposure to electric stimuli increased safety learning in male NPSR +/+ mice. This pre‐exposure effect was blocked in NPSR‐deficient male mice showing impaired, but still intact, safety learning in comparison to their NPSR +/+ and NPSR +/− littermates. There was neither a pre‐exposure nor a genotype effect in female mice. Our findings provide evidence that pre‐exposure to stress induced by electric stimuli enhances safety learning in male mice, and that NPSR‐deficiency prevents the beneficial effect of stress exposure on safety learning. We propose an inverted U‐shape relationship between stress and safety learning.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neuropeptide‐S‐receptor deficiency affects sex‐specific modulation of safety learning by pre‐exposure to electric stimuli

Kreutzmann

Khalil

Köhler

et al. 2020

Genes Brain and Behavior

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“…The more active T allele of the functional A/T single nucleotide polymorphism (SNP, rs324981) in the human gene coding for the neuropeptide S receptor (NPSR1) on chromosome 7p14 has been shown to be associated with PD, elevated anxiety sensitivity (AS), increased autonomic arousal and alterations in the emotion-potentiated startle response . The NPSR1 T allele was furthermore found to be associated with decreased prefrontal control in an emotional stroop task paradigm (Tupak et al, 2012) as well as increased amygdala activity in healthy participants (Dannlowski et al, 2011) and decreased activity in the prefrontal cortex and the ACC in patients with PD during emotional processing. The NPS system is of particular interest regarding the suggested excitatory/inhibitory dysbalance involving GABA and glutamate neurotransmission in anxiety and PD, since NPS precursor is co-expressed with glutamate in brainstem nuclei (Xu et al, 2007), NPS has been shown to alleviate neuropathological, neurochemical and behavioral changes produced by N-methyl-D-aspartate (NMDA) receptor antagonists in the murine model (Okamura et al, 2010), and an increased glutamatergic synaptic transmission to intercalated GABAergic neurons in the amygdala has been identified to accompany the effects of NPS administration on anxiety-like behavior in mice (Jungling et al, 2008).…”

Section: Introductionmentioning

confidence: 92%

Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic

Ruland

Domschke²,

Schütte

et al. 2015

European Neuropsychopharmacology

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Genetic influences on the neural and physiological bases of acute threat: A research domain criteria (RDoC) perspective

Sumner

Powers

Jovanović

2015

American J of Med Genetics Pt B

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The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: 1) neural circuits and 2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35-50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium.

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Neuropeptide S receptor gene: Fear-specific modulations of prefrontal activation

Cited by 30 publications

References 62 publications

Neuropeptide‐S‐receptor deficiency affects sex‐specific modulation of safety learning by pre‐exposure to electric stimuli

Neuropeptide‐S‐receptor deficiency affects sex‐specific modulation of safety learning by pre‐exposure to electric stimuli

Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic

Genetic influences on the neural and physiological bases of acute threat: A research domain criteria (RDoC) perspective

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