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Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety
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Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety
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Journal Article
Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety
2008
Overview
Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A
1
and A
2A
receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A
2A
(
ADORA2A
) and DRD
2
(
DRD2
) receptors. Healthy male and female individuals (
n
=102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and
ADORA2A
rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3′-flank), and
DRD2
rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected
ADORA2A
and
DRD2
polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an
ADORA2A
polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other
ADORA2A
and
DRD2
polymorphisms also contribute to responses to caffeine.
Publisher
Springer International Publishing,Nature Publishing,Nature Publishing Group
Subject
/ Adult
/ Anxiety
/ Anxiety Disorders - chemically induced
/ Anxiety Disorders - genetics
/ Anxiety Disorders - physiopathology
/ Biological and medical sciences
/ Brain Chemistry - drug effects
/ Dose-Response Relationship, Drug
/ Female
/ Genetic Predisposition to Disease - genetics
/ Genetic Variation - genetics
/ Genotype
/ Humans
/ Male
/ Medicine
/ Pharmacology. Drug treatments
/ Phosphodiesterase Inhibitors - pharmacology
/ Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
/ Psychology. Psychoanalysis. Psychiatry
/ Receptor, Adenosine A2A - drug effects
/ Receptor, Adenosine A2A - genetics
/ Receptors, Dopamine D2 - drug effects
