Tateyama M, Nagao T, Ohta S, Hirobe M, Ono H
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Eur J Pharmacol. 1993 Aug 10;240(1):51-6. doi: 10.1016/0014-2999(93)90544-r.
The inhibitory effect of 4-phenyltetrahydroisoquinoline (4-PTIQ) on methamphetamine-induced dopamine release in the rat nucleus accumbens was investigated using a brain microdialysis method. Methamphetamine (10(-6) M) infusion through a microdialysis probe induced the release of dopamine. Although the uptake inhibitors, cocaine (3 x 10(-6) M) and nomifensine (10(-6) M), failed to block dopamine release, 4-PTIQ (10(-6 M) inhibited the dopamine-releasing effect of methamphetamine. 4-PTIQ did not affect the elevation of the extracellular dopamine level induced by high concentrations of nomifensine (10(-5) M) and cocaine (3 x 10(-5) M). 4-PTIQ was the weakest inhibitor of [3H]dopamine uptake by rat striatal synaptosomes. These results suggest that 4-PTIQ is a selective antagonist against the dopamine-releasing effect of methamphetamine in the nucleus accumbens.
采用脑微透析法研究了4-苯基四氢异喹啉(4-PTIQ)对甲基苯丙胺诱导的大鼠伏隔核多巴胺释放的抑制作用。通过微透析探针注入甲基苯丙胺(10^(-6) M)可诱导多巴胺释放。尽管摄取抑制剂可卡因(3×10^(-6) M)和诺米芬辛(10^(-6) M)未能阻断多巴胺释放,但4-PTIQ(10^(-6) M)可抑制甲基苯丙胺的多巴胺释放效应。4-PTIQ不影响高浓度诺米芬辛(10^(-5) M)和可卡因(3×10^(-5) M)诱导的细胞外多巴胺水平升高。4-PTIQ是大鼠纹状体突触体对[3H]多巴胺摄取的最弱抑制剂。这些结果表明,4-PTIQ是伏隔核中甲基苯丙胺多巴胺释放效应的选择性拮抗剂。