Tran-Nguyen L T, Castañeda E, MacBeth T
Department of Psychology, Arizona State University Tempe 85287-1104, USA.
Pharmacol Biochem Behav. 1996 Sep;55(1):141-50. doi: 10.1016/0091-3057(96)00068-8.
Long-Evans rats received bilateral 6-hydroxydopamine infusions into the nucleus accumbens and were tested immediately (1 and 2 days) or after a recovery period (14 and 15 days) for changes in extracellular levels of dorsal striatal monoamines using in vivo microdialysis. Compared to controls, the monoamine metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were generally enhanced when tested immediately after 6-hydroxydopamine treatment, including spontaneous levels and those following depolarizing infusions of potassium (60 mM, 20 min) through the microdialysis probes. Following 2 weeks recovery, dopamine metabolite levels were depressed and the serotonin metabolite levels remained enhanced. D-Amphetamine sulfate (1.5 mg/kg, SC) stimulated dopamine overflow was enhanced 2 days after 6-hydroxydopamine administration, but not after 2 weeks recovery. In contrast, potassium increased dopamine overflow to the same extent as control animals regardless of recovery period following 6-hydroxydopamine. The immediate changes in striatal monoamine activity were accompanied by a potentiation of amphetamine-induced stereotyped behaviors. We suggest that transient presynaptic changes within the dorsal striatum following disruption of the ventral striatum may mediate some general aspects of loss and recovery of behavior related to the time course of 6-hydroxydopamine neurotoxicity.
将6-羟基多巴胺双侧注入Long-Evans大鼠的伏隔核，然后立即（1天和2天）或在恢复期（14天和15天）后，使用体内微透析技术检测背侧纹状体单胺细胞外水平的变化。与对照组相比，在6-羟基多巴胺处理后立即进行测试时，单胺代谢产物3,4-二羟基苯乙酸、高香草酸和5-羟基吲哚乙酸通常会升高，包括自发水平以及通过微透析探针注入钾（60 mM，20分钟）去极化后的水平。恢复2周后，多巴胺代谢产物水平降低，而5-羟色胺代谢产物水平仍升高。硫酸右旋苯丙胺（1.5 mg/kg，皮下注射）刺激的多巴胺溢出在6-羟基多巴胺给药后2天增强，但在恢复2周后未增强。相反，无论6-羟基多巴胺给药后的恢复期如何，钾使多巴胺溢出增加的程度与对照动物相同。纹状体单胺活性的即时变化伴随着苯丙胺诱导的刻板行为的增强。我们认为，腹侧纹状体破坏后背侧纹状体内短暂的突触前变化可能介导了与6-羟基多巴胺神经毒性时间进程相关的行为丧失和恢复的一些一般方面。
