腹侧纹状体 D2/3 受体可用性与冲动选择行为以及边缘皮质纹状体连接有关。
Ventral Striatal D2/3 Receptor Availability Is Associated with Impulsive Choice Behavior As Well As Limbic Corticostriatal Connectivity.
机构信息
Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Discovery Research, Biberach an der Riss, Germany.
Department of Neurology, University of Ulm, RKU, Ulm, Germany.
出版信息
Int J Neuropsychopharmacol. 2018 Jul 1;21(7):705-715. doi: 10.1093/ijnp/pyy030.
BACKGROUND
Low dopamine D2/3 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 D2/3 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 D2/3 receptor availability in the nucleus accumbens and impulsivity in a delay-discounting task where animals must choose between immediate, small-magnitude rewards and delayed, larger-magnitude rewards. Corticostriatal D2/3 receptor availability was measured in rats stratified for high and low impulsivity using in vivo [18F]fallypride positron emission tomography and ex vivo [3H]raclopride autoradiography. Resting-state functional connectivity in limbic corticostriatal networks was also assessed using fMRI.
RESULTS
Delay-discounting task impulsivity was inversely related to D2/3 receptor availability in the nucleus accumbens core but not the dorsal striatum, with higher D2/3 binding in the nucleus accumbens shell of high-impulsive rats compared with low-impulsive rats. D2/3 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 D2/3 receptor binding in the nucleus accumbens core. Thus, two related forms of waiting impulsivity-premature responding and delay intolerance in a delay-of-reward task-implicate an involvement of D2/3 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.
背景
在被试进行线索注意任务时，壳核中的多巴胺 D2/3 受体可用性较低与大鼠的高度冲动行为有关，这种行为表现为过早反应。然而，目前尚不清楚壳核中的多巴胺 D2/3 受体可用性是否同样与延迟奖励的不容忍有关，这是一种相关形式的冲动。
方法
我们使用延迟折扣任务来研究壳核中 D2/3 受体可用性与冲动性之间的关系，在该任务中，动物必须在即时、小幅度奖励和延迟、大幅度奖励之间进行选择。使用活体 [18F]fallypride 正电子发射断层扫描和离体 [3H]raclopride 放射自显影术对高和低冲动性大鼠进行分层，以测量纹状体壳核中的皮质纹状体 D2/3 受体可用性。还使用 fMRI 评估边缘纹状体网络的静息状态功能连接。
结果
延迟折扣任务的冲动性与壳核核心中的 D2/3 受体可用性呈负相关，但与背侧纹状体无关，与低冲动性大鼠相比，高冲动性大鼠壳核中的 D2/3 结合更高。D2/3 受体可用性与高冲动性大鼠与低冲动性大鼠相比，扣带回皮层和海马体之间的连接更强。
结论
我们得出的结论是，延迟折扣任务的冲动性与壳核核心中的 D2/3 受体结合率低有关。因此，两种相关形式的等待冲动——在延迟奖励任务中的过早反应和延迟不耐受——分别涉及壳核和核心中的 D2/3 受体可用性。这种分离可能是增强边缘大脑回路功能连接的因果关系或后果，并与注意力缺陷/多动障碍、药物成瘾和其他精神障碍有关。
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