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. 2010 Jul 30;329(5991):532.
doi: 10.1126/science.1185778.

Dopaminergic network differences in human impulsivity

Joshua W Buckholtz  1 , Michael T Treadway, Ronald L Cowan, Neil D Woodward, Rui Li, M Sib Ansari, Ronald M Baldwin, Ashley N Schwartzman, Evan S Shelby, Clarence E Smith, Robert M Kessler, David H Zald
Affiliations

Dopaminergic network differences in human impulsivity

Joshua W Buckholtz et al. Science. .

Abstract

Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.

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Figures

Fig. 1
Fig. 1
(A) Rendering of two separate SPMs depicting negative correlations between BIS-11 scores and D2/D3 binding and positive correlations between BIS-11 scores and amphetamine-induced DA release (corrected for multiple comparisons at the cluster-level, pcorrected < 0.05; clusters defined using a height threshold of t > 3). For the D2/D3 binding, inverse associations emerged in the DA midbrain [anteriorly in the VTA, centered at 6, −3, −11 (x, y, z; MNI space) and posteriorly in the retrorubral fields)] as well as more anteriorly in the mammillary bodies and hypothalamus (not shown). Peak coordinates for the striatal AMPH-induced DA release correlations = −16, 15, 5 (left) and 20, 23, −3 (right); cluster sizes = 167 voxels (left) and 216 voxels (right). Colorbar represents Fisher-transformed z-statistic values for the correlations (d.f. = 31). SPMs rendered on a T1-weighted MRI template brain, with cuts at z = −11 and y = 16. (B) Path analysis demonstrating that the influence of midbrain D2/D3 availability on trait impulsivity is mediated through an impact on striatal amphetamine-induced DA release. Path “A” shows path coefficients for the effect of midbrain D2/D3 binding (cluster highlighted with red circle) on striatal DA release (left/right striatum). Path “B” shows the path coefficient for the effect of striatal DA release on trait impulsivity (left/right striatum). Paths “C” and “C’” show coefficients for the total (dashed line) and direct (solid line) effects of midbrain D2/D3 binding on trait impulsivity. All coefficients standardized. Sobel test for mediation: Z = −1.94, p = 0.05, with left and right striatum modeled simultaneously.
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References

    1. Malloy-Diniz L, Fuentes D, Leite WB, Correa H, Bechara A. J Int Neuropsychol Soc. 2007 Jul;13:693. - PubMed
    1. Verdejo-Garcia A, Lawrence AJ, Clark L. Neurosci Biobehav Rev. 2008;32:777. - PubMed
    1. Barratt ES, Stanford MS, Dowdy L, Liebman MJ, Kent TA. Psychiatry Res. 1999 May 31;86:163. - PubMed
    1. Cools R, Barker RA, Sahakian BJ, Robbins TW. Neuropsychologia. 2003;41:1431. - PubMed
    1. Dalley JW, et al. Science. 2007 Mar 2;315:1267. - PMC - PubMed

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