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

Rationale/objectives Both the neuropeptide S (NPS) system and antagonism at the adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in the mediation of arousal and anxiety/panic in animal and human studies. Furthermore, a complex interaction of the neuropeptide S and the ade...

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Published in:	Psychopharmacologia Vol. 222; no. 3; pp. 533 - 541
Main Authors:	Domschke, Katharina, Klauke, Benedikt, Winter, Bernward, Gajewska, Agnes, Herrmann, Martin J., 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
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer-Verlag 01-08-2012 Springer Springer Nature B.V
Subjects:	Adenosine Adenosine A2A receptors Adult Affect Biological and medical sciences Biomedical and Life Sciences Biomedicine Caffeine Caffeine - pharmacology Emotions Female Genetic research Genotype Humans Male Medical sciences Neuropeptides - physiology Neuropharmacology Neurosciences Original Investigation Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Psychiatry Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Psychotropic drugs Receptor, Adenosine A2A - physiology Receptors, Neuropeptide - genetics Reflex, Startle - drug effects Germany NPS Emotion Acoustic startle reflex NPSR Caffeine Adenosine 2A receptor Adenosine 2A receptor · Emotion CNS stimulant Psychotropic Emotion emotionality Startle reflex Neuropeptide Respiratory analeptic Acoustic stimulus Gene Genetics Xanthine derivatives Adenosine receptor Biological receptor
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Summary:	Rationale/objectives Both the neuropeptide S (NPS) system and antagonism at the adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in the mediation of arousal and anxiety/panic in animal and human studies. Furthermore, a complex interaction of the neuropeptide S and the adenosinergic system has been suggested with administration of the adenosine A2A receptor antagonist caffeine downregulating NPS levels (Lage et al., 2006 ) and attenuating the stimulatory effects of NPS in rodents (Boeck et al., 2010 ). Methods Thus, in the present study, the impact of the functional neuropeptide S receptor (NPSR) A/T (Asn 107 Ile; rs324981) variant on affect-modulated (neutral, unpleasant, and pleasant IAPS pictures) startle response depending on the administration of 300 mg caffeine citrate was investigated in a sample of 124 ( m = 58, f = 66) healthy probands using a double-blind, placebo-controlled design. Results ANOVA revealed a significant interaction between NPSR genotype, challenge condition, and picture valence. Comparing startle magnitudes upon stimulation with neutral or emotional pictures between the placebo and caffeine condition, in AA/AT non-risk genotype carriers no significant difference was discerned, while TT risk genotype carriers showed a significantly increased startle magnitude in response to neutral stimuli ( p = .02) and a significantly decreased startle magnitude in response to unpleasant stimuli ( p = .02) in the caffeine condition as compared to the placebo condition. Conclusions In summary, the present findings — extending previous evidence from rodent studies — for the first time provide support for a complex, non-linear interaction of the neuropeptide S and adenosinergic systems affecting the affect-modulated startle response as an intermediate phenotype of anxiety in humans.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0033-3158 1432-2072
DOI:	10.1007/s00213-012-2678-0