Abercrombie E D, DeBoer P
Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA.
J Neurosci. 1997 Nov 1;17(21):8498-505. doi: 10.1523/JNEUROSCI.17-21-08498.1997.
Dopamine release can regulate striatal acetylcholine efflux in vivo through at least two receptor mechanisms: (1) direct inhibition by dopamine D2 receptors on the cholinergic neurons, and (2) excitation initiated by dopamine D1 receptors. The neuroanatomical locus of the latter population of D1 receptors and the pathway(s) involved in the expression of their influence are controversial issues. We have tested the hypothesis that D1 receptors in substantia nigra pars reticulata are involved in the excitatory component of dopaminergic actions on striatal acetylcholine output. In vivo microdialysis was used in awake rats. Infusion of the selective D1 receptor agonist R(+)-1-Phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF 38393) hydrochloride into pars reticulata of substantia nigra elicited a significant increase in striatal acetylcholine efflux. Likewise, D-amphetamine applied into pars reticulata of substantia nigra by reverse dialysis produced an elevation in acetylcholine output measured at a second microdialysis probe in the striatum. Application of D-amphetamine in the striatum by reverse dialysis elicited a decrease in striatal acetylcholine efflux that could be reversed subsequently by local application of D-amphetamine in substantia nigra pars reticulata. A 2 mg/kg intraperitoneal dose of D-amphetamine, which has no net effect on striatal acetylcholine output under control conditions, elicited a significant decrease in acetylcholine efflux when the D1 receptor antagonist R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH 23390) hydrochloride was applied simultaneously via a second microdialysis probe in substantia nigra pars reticulata. Thus, an excitatory D1-mediated influence on striatal acetylcholine output is initiated in substantia nigra pars reticulata, and this influence contributes to the effects of indirect dopaminergic agonists such as D-amphetamine on striatal acetylcholine efflux. These results indicate an important role of somatodendritic dopamine release, in addition to nerve terminal dopamine release, in the regulation of activity in basal ganglia circuits.
（1）多巴胺D2受体对胆碱能神经元的直接抑制作用，以及（2）多巴胺D1受体引发的兴奋作用。后一类D1受体的神经解剖学定位以及其发挥影响所涉及的途径是存在争议的问题。我们已经验证了以下假说：黑质网状部中的D1受体参与多巴胺能对纹状体乙酰胆碱输出的兴奋作用。在清醒大鼠中使用了体内微透析技术。向黑质网状部注入选择性D1受体激动剂盐酸R(+)-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓-7,8-二醇（SKF 38393）可使纹状体乙酰胆碱外流显著增加。同样，通过反向透析将右旋苯丙胺注入黑质网状部，可使在纹状体中第二个微透析探针处测得的乙酰胆碱输出量升高。通过反向透析将右旋苯丙胺注入纹状体可使纹状体乙酰胆碱外流减少，随后通过在黑质网状部局部应用右旋苯丙胺可使其逆转。在对照条件下对纹状体乙酰胆碱输出没有净效应的2mg/kg腹腔注射剂量的右旋苯丙胺，当通过黑质网状部中的第二个微透析探针同时应用D1受体拮抗剂盐酸R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓（SCH 23390）时，可使乙酰胆碱外流显著减少。因此，黑质网状部启动了对纹状体乙酰胆碱输出的兴奋性D1介导的影响，并且这种影响促成了间接多巴胺能激动剂（如右旋苯丙胺）对纹状体乙酰胆碱外流的作用。这些结果表明，除了神经末梢多巴胺释放外，树突体多巴胺释放在基底神经节回路活动的调节中也起着重要作用。
