Vaughn D M, Severson J A, Woodward J J, Randall P K, Riffee W H, Leslie S W, Wilcox R E
Scott-Ritchey Research Program School of Veterinary Medicine, Auburn University, AL 36849.
Brain Res. 1990 Aug 27;526(1):37-44. doi: 10.1016/0006-8993(90)90247-9.
Subchronic treatment with the dopamine agonist apomorphine produces a sensitization to the stereotypic effects of subsequent apomorphine challenge. The present study investigated the effects of this subchronic treatment on apomorphine induced stereotypic behavior and striatal dopamine synthesis, release, metabolism, and D2 receptor binding. The pretreatment, which enhanced the behavioral response to apomorphine challenge, also elevated basal dopamine synthesis and metabolism, but left the ability of a challenge dose of apomorphine to inhibit dopamine synthesis and metabolism unaltered. Thus, ongoing dopamine synthesis and extracellular levels of metabolites would be higher following apomorphine challenge in animals treated subchronically with the agonist. In contrast, neither synaptosomal dopamine release in response to depolarizing stimuli nor the density of D2 dopamine receptors was altered by the treatment. Overall, the results suggest that, while we did not find evidence of autoreceptor desensitization per se, apomorphine treatment may result in enhanced extracellular dopamine levels following dopamine agonist challenge to provide a greater stimulation of an intact dopamine receptor system.
用多巴胺激动剂阿扑吗啡进行亚慢性治疗会使动物对随后阿扑吗啡激发产生的刻板效应产生敏化。本研究调查了这种亚慢性治疗对阿扑吗啡诱导的刻板行为以及纹状体多巴胺合成、释放、代谢和D2受体结合的影响。预处理增强了对阿扑吗啡激发的行为反应，同时也提高了基础多巴胺合成和代谢，但不改变激发剂量的阿扑吗啡抑制多巴胺合成和代谢的能力。因此，在用激动剂进行亚慢性治疗的动物中，阿扑吗啡激发后持续的多巴胺合成和代谢物的细胞外水平会更高。相比之下，该治疗对去极化刺激引起的突触体多巴胺释放或D2多巴胺受体密度均无影响。总体而言，结果表明，虽然我们未发现自身受体脱敏的证据，但阿扑吗啡治疗可能导致多巴胺激动剂激发后细胞外多巴胺水平升高，从而对完整的多巴胺受体系统产生更大刺激。
