Effect of amphetamine-induced dopamine release on radiotracer binding to D1 and D2 receptors in rat brain striatal slices
Effect of amphetamine-induced dopamine release on radiotracer binding to D1 and D2 receptors in rat brain striatal slices
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DOI：
10.1007/s002100000293
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发表时间：
2000-11-01
影响因子：
3.6
通讯作者：
Volkow, ND
中科院分区：
文献类型：
--
作者：
Gifford, AN;Park, MH;Volkow, ND
正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）放射性示踪剂与纹状体中多巴胺D-2受体的体内结合可受到与内源性多巴胺竞争的影响。本研究进行，以确定是否可以观察到类似的抑制放射性示踪剂结合多巴胺受体后，药理学诱发的多巴胺释放大鼠脑纹状体切片。将纹状体切片在大量含氧Krebs盐水中孵育，并暴露于安非他明或甲基安非他明以引起切片内的多巴胺释放。安非他明和甲基安非他明，在浓度高达30 μ M，减少[H-3]雷氯必利结合在切片分别为77%和86%，与50%的抑制在1.6 μ M安非他明或3.0 μ M甲基安非他明。两种药物均未对切片中[H-3]SCH 23390的结合产生显著影响。这表明多巴胺能够干扰放射性示踪剂与D-2受体的结合，但不能干扰D-1受体。多巴胺摄取阻断剂可卡因和哌甲酯本身对[H-3]雷氯必利结合的影响相对较小，但通过抑制安非他明诱导的多巴胺释放，可显著降低低浓度（3 μ M）安非他明对[H-3]雷氯必利结合的抑制作用。在较高的安非他明浓度（30 μ M）下，[H-3]雷氯必利结合的抑制作用不被摄取阻断剂拮抗，从匀浆结合实验中获得的数据表明[H-3]的直接置换。总之，本研究中获得的数据表明，在PET和SPECT中观察到的安非他明对纹状体放射性示踪剂蓄积的影响也可以通过在体外脑切片中观察到，并且至少在低安非他明浓度下，通过与释放的多巴胺竞争来介导。
The in vivo binding of positron emission tomography (PET) and single photon emission computer tomography (SPECT) radiotracers to dopamine D-2 receptors in the striatum can be influenced by competition with endogenous dopamine. The present study was undertaken to determine if a similar inhibition of radiotracer binding to dopamine receptors could be observed following pharmacologically-evoked dopamine release in rat brain striatal slices. Striatal slices were incubated in a large volume of oxygenated Krebs saline and exposed to amphetamine or methamphetamine to evoke dopamine release within the slice. Amphetamine and methamphetamine, at concentrations up to 30 muM, reduced [H-3]raclopride binding in the slices by 77% and 86%, respectively, with 50% inhibition at 1.6 muM amphetamine or 3.0 muM methamphetamine. Neither drug produced a significant effect on binding of [H-3]SCH 23390 in the slices. This suggests that dopamine was able to interfere with radiotracer binding to D-2 but not D-1 receptors. The dopamine uptake blockers, cocaine and methylphenidate, had relatively little effect by themselves on [H-3]raclopride binding but, by inhibiting amphetamine-induced dopamine release, significantly reduced inhibition of [H-3]raclopride binding by a low (3 muM) amphetamine concentration. At a higher (30 muM) amphetamine concentration the inhibition of [H-3]raclopride binding was not antagonized by uptake blockers and data obtained from homogenate binding experiments indicated a direct displacement of [H-3]raclopride binding by amphetamine at this concentration.In conclusion the data obtained in the present study demonstrate that the effects of amphetamine on striatal radiotracer accumulation observed in PET and SPECT can also be observed in brain slices in vitro and, at least at low amphetamine concentrations, are mediated by competition with released dopamine.