Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "high".-猫眼课题宝

DOI：

发表时间：

1999

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The Journal of pharmacology and experimental therapeutics

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其他

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作者：

N. D. Volkow;N. D. Volkow;Gene-Jack Wang;Joanna S. Fowler;S. Gatley;J. Logan;Yu-Shin Ding;S. Dewey;R. Hitzemann;A. Gifford;N. Pappas

可卡因和哌甲酯的增强作用与其阻断多巴胺转运蛋白（DAT）的能力有关。我们之前使用正电子发射断层扫描 (PET) 表明，静脉注射可卡因会诱导显着水平的 DAT 阻断，这与可卡因滥用者自我报告的“高”强度相关。在这项研究中，我们测量了静脉注射哌醋甲酯后的 DAT 占用率，并评估它们是否也与“高”相关。在接受不同剂量哌醋甲酯测试的八名正常对照受试者中，使用[11C]可卡因作为 DAT 配体，通过 PET 测量静脉内 MP 对 DAT 的占用。 [11C]可卡因在纹状体中的分布体积与小脑中的分布体积之比（对应于Bmax/Kd+1）被用作DAT可用性的衡量标准。同时，对“高”的自我报告进行了测量。哌醋甲酯对 DAT 产生剂量依赖性阻断作用，估计 ED50 为 0.075 mg/kg。 DAT 占用率与“高”显着相关 (p <.03)。然而，八名受试者中的四名尽管具有显着水平的 DAT 封锁，但并未感知到“高”。哌醋甲酯在阻断人脑中的 DAT 方面与可卡因一样有效（可卡因 ED50 = 0.13 mg/kg），并且与可卡因一样，DAT 阻断也与“高”相关。然而，事实上，尽管有显着的 DAT 封锁，但有些受试者并未经历“高”，这表明 DAT 封锁虽然必要，但不足以产生“高”。

The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Using positron emission tomography (PET), we previously showed that intravenous cocaine induced a significant level of DAT blockade, which was associated with the intensity for self-reports of "high" in cocaine abusers. In this study, we measured DAT occupancies after intravenous methylphenidate and assessed whether they also were associated with the "high". Occupation of DAT by intravenous MP was measured with PET using [11C]cocaine, as a DAT ligand, in eight normal control subjects tested with different methylphenidate doses. The ratio of the distribution volume of [11C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd + 1, was used as measure of DAT availability. In parallel, self-reports of "high" were measured. Methylphenidate produced a dose-dependent blockade of DAT with an estimated ED50 of 0.075 mg/kg. DAT occupancies were significantly correlated with the "high" (p <.03). However, four of the eight subjects, despite having significant levels of DAT blockade, did not perceive the "high". Methylphenidate is as effective as cocaine in blocking DAT in the human brain (cocaine ED50 = 0.13 mg/kg), and DAT blockade, as for cocaine, was also associated with the "high". However, the fact that there were subjects who despite significant DAT blockade did not experience the "high" suggests that DAT blockade, although necessary, is not sufficient to produce the "high".

Blockade of striatal dopamine transporters by intravenous methylphenidate is not sufficient to induce self-reports of "high".

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