Blaha C D, Winn P
Department of Psychology, University of British Columbia, Vancouver, Canada.
J Neurosci. 1993 Mar;13(3):1035-44. doi: 10.1523/JNEUROSCI.13-03-01035.1993.
The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham-operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.
运用体内计时电流法和脑内微透析技术，研究了向乌拉坦麻醉大鼠黑质致密部微量注射胆碱能药物对其背内侧纹状体前部多巴胺（DA）流出的影响。在黑质微量注射胆碱能激动剂尼古丁或卡巴胆碱后，纹状体中观察到计时电流信号增加，表明DA流出呈剂量依赖性增强。通过向黑质内注入胆碱酯酶抑制剂新斯的明来提高黑质中乙酰胆碱（ACh）的细胞外浓度，也导致与纹状体中DA溢出相对应的计时电流信号增加。新斯的明对纹状体中DA流出的这些刺激作用通过体内微透析得到证实。与假手术对照动物相比，脑桥脚被盖核（PPTg）的喹啉酸损伤导致黑质内新斯的明对纹状体中DA流出的刺激作用减弱。相反，这些处理导致纹状体DA流出增强，以响应黑质内注入直接ACh受体激动剂尼古丁。综合这些数据表明，PPTg胆碱能神经元通过调节大鼠黑质中DA神经元的活动间接参与调节纹状体的活动。
