Abstract:
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.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Domschke K,Klauke B,Winter B,Gajewska A,Herrmann MJ,Warrings B,Mühlberger A,Wosnitza K,Dlugos A,Naunin S,Nienhaus K,Fobker M,Jacob C,Arolt V,Pauli P,Reif A,Zwanzger P,Deckert Jdoi
10.1007/s00213-012-2678-0subject
Has Abstractpub_date
2012-08-01 00:00:00pages
533-41issue
3eissn
0033-3158issn
1432-2072journal_volume
222pub_type
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