Addition of a 5‐HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP‐CIT binding to dopamine transporters in rat frontal cortex and hippocampus
Addition of a 5‐HT receptor agonist to methylphenidate potentiates the reduction of [123I]FP‐CIT binding to dopamine transporters in rat frontal cortex and hippocampus
复制标题
在哌醋甲酯中添加 5-HT 受体激动剂可增强大鼠额叶皮层和海马中 [123I]FP-CIT 与多巴胺转运蛋白结合的减少
作者：
L. Reneman;K. D. de Bruin;J. Lavalaye;W. Gunning;J. Booij
安非他明和相关药物的神经毒性潜力已有充分的文献记载。然而，哌甲酯，一种用于治疗注意力缺陷多动障碍的安非他明衍生物，已知可以增加突触多巴胺（DA）水平，似乎缺乏神经毒性潜力。据推测，多巴胺能和多巴胺能系统参与安非他明衍生物的神经毒性。本研究的目的是评价哌醋甲酯的神经毒性潜力，并测试对多巴胺能系统的刺激是否会赋予哌醋甲酯对DA或5-羟色胺（5-HT）神经元的神经毒性。此外，本研究旨在评价在使用哌甲酯和5-HT-作用剂的个体中进行未来SPECT研究的必要性。因此，我们使用适合SPECT成像的放射性配体（[123 I]β-CIT和[123 I]FP-CIT）测量了大鼠脑中的单胺能转运蛋白。各组大鼠用哌醋甲酯或生理盐水处理4天。其他组接受选择性5-HT 2受体激动剂奎帕嗪或选择性5-HT再摄取阻滞剂氟西汀单独或与哌甲酯联合治疗。在末次给药后5天进行结合研究。在第二个实验中，哌醋甲酯与奎帕嗪的组合与对照组一起沿着被重新测试。在该实验中，在药物处理后2周（而不是5天）估计单胺能末端密度。给药后5天（而非2周），在哌甲酯联合喹帕嗪给药大鼠的额叶皮质和海马中观察到特异性[123 I] FP-CIT结合显著降低。这些变化可能不反映额叶皮质和海马DA终末标记物的神经毒性变化，而是DA转运体的代偿性下调。这些结果表明，在使用哌甲酯的患者中，伴随使用直接激活5-HT 2受体的药物可能会产生有害影响。Synapse 39：193-200，2001年。© 2001 Wiley利斯公司
The neurotoxic potential of amphetamine and related drugs is well documented. However, methylphenidate, an amphetamine derivative used in the treatment of attention deficit hyperactivity disorder, and known to increase synaptic dopamine (DA) levels, seems to lack neurotoxic potential. It is hypothesized that both dopaminergic and serotonergic systems are involved in the neurotoxicity of amphetamine derivatives. The purpose of the present study was to evaluate the neurotoxic potential of methylphenidate and to test whether stimulation of the serotonergic system may confer neurotoxic properties to methylphenidate for DA or serotonin (5‐HT) neurons. In addition, the present study was undertaken to evaluate the necessity to perform future SPECT studies in individuals using both methylphenidate and 5‐HT‐acting agents. We therefore measured monoaminergic transporters in rat brain using radioligands suitable for SPECT imaging ([123I]β‐CIT and [123I]FP‐CIT). Groups of rats were treated with methylphenidate or saline for 4 days. Additional groups were treated with the selective 5‐HT2 receptor agonist quipazine or the selective 5‐HT reuptake blocker fluoxetine, alone or in combination with methylphenidate. Binding studies were performed 5 days after the last treatment. In a second experiment, methylphenidate in combination with quipazine, along with a control group, was retested. In this experiment, monoaminergic terminal density was estimated 2 weeks (rather than 5 days) after drug treatment. Five days, but not 2 weeks, after treatment a significant reduction in specific [123I]FP‐CIT binding was observed in the frontal cortex and hippocampus of rats treated with methylphenidate in combination with quipazine. These changes probably do not reflect neurotoxic changes of frontal cortex and hippocampal DA terminal markers, but a compensatory downregulation of DA transporters. These findings suggest potential harmful effects of concomitant use of drugs directly activating 5‐HT2 receptors in patients using methylphenidate. Synapse 39:193–200, 2001. © 2001 Wiley‐Liss, Inc.
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3,4-亚甲二氧基甲基苯丙胺、血清素和记忆。
DOI：
--
发表时间：
1993
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Ricaurte,GA;Markowska,AL;Wenk,GL;Hatzidimitriou,G;Wlos,J;Olton,DS
通讯作者：
Olton,DS
血清素药物对多种脑血清素受体的选择性。
影响因子：
5.8
作者：
Titeler,M;Lyon,RA;Davis,KH;Glennon,RA
通讯作者：
Glennon,RA
芬氟拉明的食欲抑制和血清素神经毒性是分开的。
影响因子：
5
作者：
McCann,UD;Yuan,J;Ricaurte,GA
通讯作者：
Ricaurte,GA
5-HT2 受体介导的多巴胺合成增强和中枢血清素能缺陷。
影响因子：
5
作者：
Huang,X;Nichols,DE
通讯作者：
Nichols,DE
影响因子：
5
作者：
GUDELSKY, GA;YAMAMOTO, BK;NASH, JF
通讯作者：
NASH, JF