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首页> 外文期刊>The European Journal of Neuroscience >Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry.
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Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry.

机译：可卡因自我管理导致对边缘和运动回路中可卡因攻击的时间反应发生改变。

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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.
机译：长期使用可卡因与大脑新陈代谢，电路和受体特性的持久改变有关。我们使用神经影像学和药理磁共振成像技术评估了经过28天训练后可按固定比例5强化时间表自我给药可卡因的动物和生理盐水轭的对照对可卡因（0.5 mg / kg）的反应变化。可卡因的禁欲。我们拟合了全血半最大值（FWHM）和峰值CBV反应的脑血容量（CBV）曲线。与前额内侧皮层（mPFC）和尾状/丘脑（CPu）中的盐水处理对照相比，可卡因自给药（SA）动物的响应曲线的FWHM显着增加，并且峰值CBV增加在M1运动皮层，CPu和pedunculopontine被盖核中。功能连接性分析显示，在急性可卡因攻击后，尤其是在S1，mPFC和丘脑中，可卡因SA大鼠的相关性增加。由于假定长期服用可卡因后D3受体的表达会增加，因此我们还检查了对0.2 mg / kg D3优选激动剂7-羟基-N，N-二-正丙基-2-氨基四氢萘酚（7-OHDPAT）的响应）。可卡因SA动物对这种药物的总体CBV反应降低，但苍白球除外。下丘脑显示出对可卡因攻击的负CBV变化，与D3激动剂相似，并且在可卡因SA动物中的响应比对照组小。鉴于先前用药理磁共振成像观察到的脑血流动力学与多巴胺动力学之间的良好耦合，这些数据表明，多巴胺在前额叶皮层中的持久性增强可能是慢性可卡因使用后观察到的某些行为改变的原因。

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