Ventral Striatal D2/3 Receptor Availability Is Associated with Impulsive Choice Behavior As Well As Limbic Corticostriatal Connectivity

被引：32

作者：

Barlow, Rebecca L. ^{[1
]}

Gorges, Martin ^{[2
]}

Wearn, Alfie ^{[1
]}

Niessen, Heiko G. ^{[3
]}

Kassubek, Jan ^{[2
]}

Dalley, Jeffrey W. ^{[4
,5
]}

Pekcec, Anton ^{[1
]}

机构：

[1] Boehringer Ingelheim Pharma GmbH & Co KG, CNS Discovery Res, Birkendorfer Str 65, D-88397 Biberach, Germany

[2] Univ Ulm, RKU, Dept Neurol, Ulm, Germany

[3] Boehringer Ingelheim Pharma GmbH & Co KG, Translat Med & Clin Pharmacol, Biberach, Germany

[4] Univ Cambridge, Dept Psychol, Cambridge, England

[5] Univ Cambridge, Dept Psychiat, Cambridge, England

来源：

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY | 2018年 / 21卷 / 07期

关键词：

delay discounting; dopamine D-2/3 receptor; impulsivity; nucleus accumbens; resting-state fMRI; functional connectivity; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS CORE; ORBITOFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; METHAMPHETAMINE DEPENDENCE; RESPONSE-INHIBITION; DOUBLE-DISSOCIATION; COCAINE; NETWORKS;

D O I：

10.1093/ijnp/pyy030

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Low dopamine D-2/3 receptor availability in the nucleus accumbens shell is associated with highly impulsive behavior in rats as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D-2/3 receptor availability in the nucleus accumbens is equally linked to intolerance for delayed rewards, a related form of impulsivity. Methods: We investigated the relationship between D-2/3 receptor availability in the nucleus accumbens and impulsivity in a delay-discounting task where animals must choose between immediate, small-magnitude rewards and delayed, largermagnitude rewards. Corticostriatal D-2/3 receptor availability was measured in rats stratified for high and low impulsivity using in vivo [F-18] fallypride positron emission tomography and ex vivo [H-3] raclopride autoradiography. Resting-state functional connectivity in limbic corticostriatal networks was also assessed using fMRI. Results: Delay-discounting task impulsivity was inversely related to D-2/3 receptor availability in the nucleus accumbens core but not the dorsal striatum, with higher D-2/3 binding in the nucleus accumbens shell of high-impulsive rats compared with low-impulsive rats. D(2/)3 receptor availability was associated with stronger connectivity between the cingulate cortex and hippocampus of high-vs low-impulsive rats. Conclusions: We conclude that delay-discounting task impulsivity is associated with low D-2/3 receptor binding in the nucleus accumbens core. Thus, two related forms of waiting impulsivity-premature responding and delay intolerance in a delay-ofreward task-implicate an involvement of D-2/3 receptor availability in the nucleus accumbens shell and core, respectively. This dissociation may be causal or consequential to enhanced functional connectivity of limbic brain circuitry and hold relevance for attention-deficit/hyperactivity disorder, drug addiction, and other psychiatric disorders.

引用

页码：705 / 715

页数：11

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