Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward.
Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study was designed to investigate the influence of the DRD2 TaqIA polymorphism and the selective D2 receptor agonist bromociptine on the activation of the reward system by means of functional magnetic resonance imaging (fMRI). In a double-blind crossover study with 24 participants we found an increase of reward system activation from placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore, only A1 carrier showed an increase of performance under bromocriptine. The results are interpreted as reflecting a specific sensitivity for dopamine agonists in persons carrying an A1 allele and may complement actual data and theories of the development of addiction disorders postulating a higher genetic risk for substance abuse in carrier of the A1 allele.
Kirsch
Peter
P
Center for Psychiatry, Justus-Liebig-University Giessen, Am Steg 28, D-35385 Giessen, Germany. peter.kirsch@psychiat.med.uni-giessen.de
Reuter
Martin
M
Mier
Daniela
D
Lonsdorf
Tina
T
Stark
Rudolf
R
Gallhofer
Bernd
B
Vaitl
Dieter
D
Hennig
Jürgen
J
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D001971:Bromocriptine / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D030141:Feedback, Psychological / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood; D011110:Polymorphism, Genetic; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012201:Reward
D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D010100:Oxygen