Nash J F, Yamamoto B K
Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106-5000.
Brain Res. 1993 Nov 5;627(1):1-8. doi: 10.1016/0006-8993(93)90741-5.
A single administration of D-amphetamine and iprindole has been reported to produce selective, long-lasting decreases in brain dopamine (DA) content because of axon terminal degeneration. It has been found that the noncompetitive glutamate (GLU) antagonist, MK 801, blocks D-amphetamine-induced DA depletion in iprindole-treated rats. In the present study, the effect of D-amphetamine (9.2 mg/kg) and iprindole (10 mg/kg) on the extracellular concentrations of DA and GLU was determined in the striatum of awake, freely moving rats by the use of in vivo microdialysis. D-Amphetamine significantly increased DA and GLU efflux in the striatum of iprindole-treated rats as compared to the vehicle-treated group. The increase in the extracellular concentration of GLU occurred 4-6 hr following drug administration. The concentration of DA was decreased significantly in the striatum of D-amphetamine and iprindole-treated rats 7 days following administration as compared to the vehicle-treated group. Inhibition of tyrosine hydroxylase after alpha-methylparatyrosine (150 mg/kg) administration attenuated D-amphetamine-induced DA and GLU release. The DA antagonist, haloperidol (1 mg/kg), blocked D-amphetamine-induced GLU release without affecting the increase in the extracellular concentration of DA produced by the combination of D-amphetamine and iprindole. Both alpha-methylparatyrosine and haloperidol blocked the depletion of DA in the striatum 7 days after D-amphetamine and iprindole as compared to the vehicle group. In addition, administration of MK-801 (2 mg/kg) 2 hr after D-amphetamine significantly attenuated the long-term (7 day) decrease in striatal DA content produced by the combination of D-amphetamine and iprindole.2+
据报道，单次给予右旋苯丙胺和茚满丙二胺会因轴突终末变性而导致脑内多巴胺（DA）含量出现选择性、持久的降低。研究发现，非竞争性谷氨酸（GLU）拮抗剂MK 801可阻断茚满丙二胺处理的大鼠中右旋苯丙胺诱导的DA耗竭。在本研究中，通过体内微透析法测定了清醒、自由活动大鼠纹状体中右旋苯丙胺（9.2 mg/kg）和茚满丙二胺（10 mg/kg）对DA和GLU细胞外浓度的影响。与溶剂处理组相比，右旋苯丙胺显著增加了茚满丙二胺处理大鼠纹状体中的DA和GLU流出量。药物给药后4 - 6小时，GLU细胞外浓度升高。与溶剂处理组相比，右旋苯丙胺和茚满丙二胺处理大鼠给药7天后纹状体中DA浓度显著降低。给予α-甲基对酪氨酸（150 mg/kg）后抑制酪氨酸羟化酶可减弱右旋苯丙胺诱导的DA和GLU释放。DA拮抗剂氟哌啶醇（1 mg/kg）可阻断右旋苯丙胺诱导的GLU释放，而不影响右旋苯丙胺与茚满丙二胺联合产生的DA细胞外浓度升高。与溶剂组相比，α-甲基对酪氨酸和氟哌啶醇均阻断了右旋苯丙胺和茚满丙二胺给药7天后纹状体中DA的耗竭。此外，在右旋苯丙胺给药2小时后给予MK-801（2 mg/kg）可显著减弱右旋苯丙胺与茚满丙二胺联合产生的纹状体DA含量长期（7天）降低。
