Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry
Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry
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DOI：
10.1111/j.1460-9568.2011.07806.x
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发表时间：
2011-09-01
影响因子：
3.4
通讯作者：
Jenkins, Bruce G.
中科院分区：
文献类型：
--
作者：
Chen, Y. Iris;Famous, K.;Jenkins, Bruce G.
长期使用可卡因与脑代谢、回路和受体特性的持久改变有关。我们使用神经成像和药理学磁共振成像来评估在可卡因戒断28天后，经训练以固定比例5的强化计划自我服用可卡因的动物，以及盐碱对照，对可卡因（0.5 mg/kg）的反应变化。我们拟合了全宽半最大值（FWHM）和CBV峰值反应的脑血容量（CBV）曲线。与盐水对照相比，可卡因自我给药（SA）动物的反应曲线FWHM在内侧前额叶皮层（mPFC）和尾状/壳核（CPu）显著增加，M1运动皮层、CPu和桥柄脑被盖核的CBV峰值增加。功能连通性分析显示，在急性可卡因刺激下，可卡因SA大鼠的相关性增加，特别是在S1、mPFC和丘脑。由于假定慢性可卡因给药后D3受体的表达会增加，我们还检查了对0.2 mg/kg的D3偏好激动剂7-羟基-n， n-二-n-丙基-2-氨基四萘林（7-OHDPAT）的反应。除苍白球外，可卡因SA动物对这种药物的总体CBV反应降低。下丘脑在可卡因刺激下表现出负的CBV变化，与D3激动剂相似，并且在可卡因SA动物中表现出比对照组较小的反应。鉴于先前通过药理学磁共振成像观察到的脑血流动力学与多巴胺动力学的良好耦合，这些数据表明，前额叶皮层多巴胺持久性的增加可能是慢性可卡因使用后观察到的一些行为改变的原因。
Chronic use of cocaine is associated with lasting alterations in brain metabolism, circuitry, and receptor properties. We used neuroimaging with pharmacological magnetic resonance imaging to assess alterations in response to cocaine (0.5 mg/kg) in animals trained to self-administer cocaine on a fixed-ratio 5 schedule of reinforcement, as well as saline-yoked controls, after 28 days of cocaine abstinence. We fitted the cerebral blood volume (CBV) curves for full-width half-maximum (FWHM) as well as peak CBV response. There were significant increases in the FWHM of the response curves in the cocaine self-administering (SA) animals as compared with saline-yoked controls in the medial prefrontal cortex (mPFC) and the caudate/putamen (CPu), and increases in peak CBV in the M1 motor cortex, CPu, and pedunculopontine tegmental nucleus. Functional connectivity analysis showed increased correlations in the cocaine SA rats upon acute cocaine challenge, especially in the S1, mPFC, and thalamus. As D3 receptor expression is postulated to increase following chronic cocaine administration, we also examined the response to 0.2 mg/kg of the D3-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT). Cocaine SA animals showed a decreased overall CBV response to this drug, except in the globus pallidus. The hypothalamus showed a negative CBV change in response to cocaine challenge, similar to that noted with the D3 agonist, and showed a smaller response in the cocaine SA animals than in the controls. Given the good coupling of cerebral hemodynamics with dopamine dynamics previously observed with pharmacological magnetic resonance imaging, these data suggest that increased persistence of dopamine in the prefrontal cortex may be responsible for some of the behavioral alterations observed subsequent to chronic cocaine use.