D2 antidopaminergic modulation of frontal lobe function in healthy human subjects.
BACKGROUND
Although the major principles of dopamine (DA) signaling have been well described previously, its precise modulatory impact on the prefrontal cortex (PFC) in humans is poorly understood. Two major neurophysiological models propose segregated functional circuits on the systems level as well as D(1) and D(2) receptor-dependent processing states on the cellular level (two-state model).


METHODS
We examined the predictive validity of these models in 10 healthy male volunteers with a haloperidol challenge (HLP). Cortico-striatal-thalamo-cortical (CSTC) motor loop functions were examined during functional magnetic resonance imaging (fMRI) with a sequential finger opposition task. Neuropsychological implications of the two-state model were evaluated with a test battery of D(1)- or D(2)-sensitive prefrontal measures.


RESULTS
Analysis of fMRI data revealed a significant HLP-induced blood oxygen level dependent-signal decrease in the sensorimotor striatum and a lateralized activation loss of ipsilateral higher order motor cortices and contralateral cerebellum. Neuropsychological evaluation demonstrated a preferential impairment of D(2)-sensitive functions, whereas D(1) or non-dopaminergic domains were unaffected.


CONCLUSIONS
Our data support the hypothesis that mesocortical D(1) and D(2) receptors exert differential influences in the PFC for cognitive function, but the nigrostriatal CSTC network model for the motor domain could not be confirmed.
Tost
Heike
H
Department of Psychiatry and Psychotherapy, University of Heidelberg, Germany. tost@zi-mannheim.de
Meyer-Lindenberg
Andreas
A
Klein
Sabine
S
Schmitt
Andrea
A
Höhn
Fabian
F
Tenckhoff
Amrei
A
Ruf
Matthias
M
Ende
Gabriele
G
Rietschel
Marcella
M
Henn
Fritz A
FA
Braus
Dieter F
DF
D000328:Adult; D001931:Brain Mapping; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005625:Frontal Lobe / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010100:Oxygen / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000502:physiology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D006220:Haloperidol; D010100:Oxygen