TY - JOUR
T1 - Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation
AU - Domschke, Katharina
AU - Klauke, Benedikt
AU - Winter, Bernward
AU - Gajewska, Agnes
AU - Herrmann, Martin J.
AU - Warrings, Bodo
AU - Muehlberger, Andreas
AU - Wosnitza, Katherina
AU - Dlugos, Andrea
AU - Naunin, Swantje
AU - Nienhaus, Kathrin
AU - Fobker, Manfred
AU - Jacob, Christian
AU - Arolt, Volker
AU - Pauli, Paul
AU - Reif, Andreas
AU - Zwanzger, Peter
AU - Deckert, Juergen
PY - 2012/8
Y1 - 2012/8
N2 - 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).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.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.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.
AB - 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).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.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.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.
KW - NPS
KW - NPSR
KW - Caffeine
KW - Adenosine 2A receptor
KW - Emotion
KW - Acoustic startle reflex
U2 - 10.1007/s00213-012-2678-0
DO - 10.1007/s00213-012-2678-0
M3 - Article
C2 - 22399050
SN - 0033-3158
VL - 222
SP - 533
EP - 541
JO - Psychopharmacology
JF - Psychopharmacology
IS - 3
ER -