D2 antidopaminergic modulation of frontal lobe function in healthy human subjects

Tost, H., Meyer-Lindenberg, A., Klein, S., Schmitt, A., Hohn, F., Tenckhoff, A., Ruf, M., Ende, G., Rietschel, M., Henn, F. A., Braus, D. F. (December 2006) D2 antidopaminergic modulation of frontal lobe function in healthy human subjects. Biol Psychiatry, 60 (11). pp. 1196-205. ISSN 0006-3223 (Print)0006-3223 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/16950215
DOI: 10.1016/j.biopsych.2006.04.014

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Adult Brain Mapping Dopamine Antagonists/pharmacology Frontal Lobe/blood supply/drug effects/ physiology Haloperidol/pharmacology Humans Image Processing, Computer-Assisted/methods Magnetic Resonance Imaging/methods Male Neural Pathways/blood supply/drug effects/physiology Neuropsychological Tests/statistics & numerical data Oxygen/blood Receptors, Dopamine D2/ antagonists & inhibitors/ physiology
Subjects: Investigative techniques and equipment
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dopaminergic neuron
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dopaminergic neuron
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dopaminergic neuron
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > dopaminergic neuron
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > dopaminergic neuron
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > dopaminergic neuron

organs, tissues, organelles, cell types and functions > tissues types and functions > frontal lobe
organism description > animal > mammal > primates > hominids > human
Investigative techniques and equipment > magnetic resonance imaging
organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Henn lab
Depositing User: Matt Covey
Date: 1 December 2006
Date Deposited: 01 Mar 2013 17:24
Last Modified: 01 Mar 2013 17:24
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27658

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