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

Domschke, Katharina; Klauke, Benedikt; Winter, Bernward; Gajewska, Agnes; Warrings, Bodo; Mühlberger, Andreas; Wosnitza, Katherina; Dlugos, Andrea; Naunin, Swantje; Nienhaus, Kathrin; Fobker, Manfred; Jacob, Christian; Arolt, Volker; Pauli, Paul; Reif, Andreas; Zwanzger, Peter; Deckert, Jürgen

doi:10.1007/s00213-012-2678-0

Cited by 22 publications

(16 citation statements)

References 59 publications

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“…As the Ile 107 NPSR1 is associated with panic and startle responses in humans (Domschke et al, 2012), we finally determined whether intracerebroventricular NPS administration could reduce conditioned fear expression and facilitate the impaired fear extinction, respectively, in HAB rodents, as shown before in nonselected mice (Jüngling et al, 2008;Meis et al, 2008). Indeed, intracerebroventricular NPS administration was able to reduce the exaggerated fear expression seen in mHABs and to accelerate fear extinction in rHABs.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, Npsr1 is located in a chromosomal region linked to panic disorder, and a corresponding single nucleotide poly-morphism (SNP; Asn 107 Ile-rs324981) has been associated with increased risk of the overinterpretation of fear (Okamura et al, 2007;Donner et al, 2010;Raczka et al, 2010;Domschke et al, 2011). However, while the preclinical findings to date suggest that increasing NPS levels within the brain reduces anxiety and fear responses, the human Ile 107 receptor variant exhibits increased surface receptor expression and a 10-fold higher NPSinduced signaling response than the Asn 107 variant Bernier et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Selective Breeding for High Anxiety Introduces a Synonymous SNP That Increases Neuropeptide S Receptor Activity

Slattery¹,

Naik

Grund³

et al. 2015

J. Neurosci.

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Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behavior (HAB) versus low anxiety-related behavior, and, thereafter, determined the effect of central NPS administration on anxiety-and fear-related behavior. The HAB phenotype was accompanied by lower basal NPS receptor (Npsr1) expression, which we could confirm via in vitro dual luciferase promoter assays. Assessment of shorter Npsr1 promoter constructs containing a sequence mutation that introduces a glucocorticoid receptor transcription factor binding site, confirmed via oligonucleotide pull-down assays, revealed increased HAB promoter activity-an effect that was prevented by dexamethasone. Analogous to the human NPSR1 risk isoform, functional analysis of a synonymous single nucleotide polymorphism in the coding region of HAB rodents revealed that it caused a higher cAMP response to NPS stimulation.AssessmentofthebehavioralconsequenceofthesedifferencesrevealedthatintracerebroventricularNPSreversedthehyperanxiety of HAB rodents as well as the impaired cued-fear extinction in HAB rats and the enhanced fear expression in HAB mice, respectively. These results suggest that alterations in the NPS system, conserved across rodents and humans, contribute to innate anxiety and fear, and that HAB rodents are particularly suited to resolve the apparent discrepancy between the preclinical and clinical findings to date.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective Breeding for High Anxiety Introduces a Synonymous SNP That Increases Neuropeptide S Receptor Activity

Slattery¹,

Naik

Grund³

et al. 2015

J. Neurosci.

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“…A disturbed or hypersensitive arousal–anxiety relationship might be particularly relevant in individuals with anxiety disorders where hypervigilance and misinterpretation of heightened arousal is crucial (Craske & Simos, ). Consistent with this view, genetic studies have revealed a relationship of the more active rs324981 T allele of the neuropeptide S receptor ( NPSR1 ) gene with anxiety sensitivity, physiological arousal, startle response, executive function and panic disorder, particularly in women (Okamura et al ., ; Domschke et al ., , ; Beste et al ., ; Klauke et al ., ).…”

Section: Molecular Biology/geneticsmentioning

confidence: 99%

Arousal and the attentional network in panic disorder

Geiger

Neufang

Stein

et al. 2014

Human Psychopharmacology

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Although a great deal of information about the neurobiology of panic disorder is now available, there is a need for an updated etiological model integrating recent findings on the neurobiology of the arousal system and its relationship with higher cortical functions in panic disorder. The current mini-review presents psychophysiological, molecular biological/genetic and functional neuroimaging evidence for dysfunction in major arousal systems of the brain. Such dysfunction may influence the development of panic disorder by precipitating autonomic bodily symptoms and at the same time increasing vigilance to these sensations by modulating cortical attentional networks. A multilevel model of arousal, attention and anxiety-including the norepinephrine, orexin, neuropeptide S and caffeine-related adenosine systems-may be useful in integrating a range of data available on the pathogenesis of panic disorder.

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“…Genotyping for the functional neuropeptide S receptor (NPSR1) A/T (N 107 I) variant (rs324981) was performed according to published protocols Domschke et al, 2012). Genotypes were determined by investigators blinded for phenotypes and independently by two investigators.…”

Section: Genotypingmentioning

confidence: 99%

Modulation of prefrontal functioning in attention systems by NPSR1 gene variation

et al. 2015

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

Cited by 22 publications

References 59 publications

Selective Breeding for High Anxiety Introduces a Synonymous SNP That Increases Neuropeptide S Receptor Activity

Selective Breeding for High Anxiety Introduces a Synonymous SNP That Increases Neuropeptide S Receptor Activity

Arousal and the attentional network in panic disorder

Modulation of prefrontal functioning in attention systems by NPSR1 gene variation

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