Neurobehavioral Precursors of Compulsive Cocaine Seeking in Dual Frontostriatal Circuits.
Neurobehavioral Precursors of Compulsive Cocaine Seeking in Dual Frontostriatal Circuits.
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DOI：
10.1016/j.bpsgos.2023.06.001
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发表时间：
2024-01
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影响因子：
--
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中科院分区：
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只有一些以娱乐方式使用药物的个体最终发展为物质使用障碍，其部分特征在于刚性参与药物觅食行为（药物寻求），这通常在面对不良后果时保持（即，是强迫性的）。这种个体脆弱性的神经行为决定因素尚未完全阐明。使用一项涉及39只雄性大鼠的前瞻性纵向研究，我们将易受刺激剂使用障碍（冲动性和粘性）和弹性（符号跟踪和感觉寻求/对新奇事物的运动反应）的行为特征的多维表征与磁共振成像相结合，以确定在药物初治受试者中后来出现强迫性药物寻求的结构和功能大脑相关性。我们开发了一种新的行为程序，以调查在无药物状态下，在药物配对巴甫洛夫条件刺激的条件强化特性控制下，长期寻求可卡因的受试者在面对惩罚时坚持寻求药物行为的个体倾向。在未用药的大鼠中，出现强迫性可卡因寻求倾向的特征是前额叶皮层和后背内侧纹状体之间的行为粘性相关功能连接不足，以及边缘下皮层、前额叶和背内侧核中冲动相关结构改变。这些发现表明，发展强迫性可卡因寻求行为的脆弱性源于两个不同的皮质纹状体系统中预先存在的结构或功能变化，这些变化是冲动控制和目标导向行为缺陷的基础。
Only some individuals who use drugs recreationally eventually develop a substance use disorder, characterized in part by the rigid engagement in drug foraging behavior (drug seeking), which is often maintained in the face of adverse consequences (i.e., is compulsive). The neurobehavioral determinants of this individual vulnerability have not been fully elucidated. Using a prospective longitudinal study involving 39 male rats, we combined multidimensional characterization of behavioral traits of vulnerability to stimulant use disorder (impulsivity and stickiness) and resilience (sign tracking and sensation seeking/locomotor reactivity to novelty) with magnetic resonance imaging to identify the structural and functional brain correlates of the later emergence of compulsive drug seeking in drug-naïve subjects. We developed a novel behavioral procedure to investigate the individual tendency to persist in drug-seeking behavior in the face of punishment in a drug-free state in subjects with a prolonged history of cocaine seeking under the control of the conditioned reinforcing properties of a drug-paired Pavlovian conditioned stimulus. In drug-naïve rats, the tendency to develop compulsive cocaine seeking was characterized by behavioral stickiness–related functional hypoconnectivity between the prefrontal cortex and posterior dorsomedial striatum in combination with impulsivity-related structural alterations in the infralimbic cortex, anterior insula, and nucleus accumbens. These findings show that the vulnerability to developing compulsive cocaine-seeking behavior stems from preexisting structural or functional changes in two distinct corticostriatal systems that underlie deficits in impulse control and goal-directed behavior.
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影响因子：
7.6
作者：
Cannella, Nazzareno;Halbout, Briac;Spanagel, Rainer
通讯作者：
Spanagel, Rainer
影响因子：
2.3
作者：
Anthony, James C.;Warner, Lynn A.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
10.6
作者：
Ersche, Karen D.;Turton, Abigail J.;Pradhan, Shachi;Bullmore, Edward T.;Robbins, Trevor W.
通讯作者：
Robbins, Trevor W.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
2.7
作者：
Chudasama, Y;Passetti, F;Robbins, TW
通讯作者：
Robbins, TW