Zahm D S, Williams E S, Krause J E, Welch M A, Grosu D S
Department of Anatomy and Neurobiology, St. Louis University School of Medicine, Missouri 63104, USA.
J Comp Neurol. 1998 Nov 2;400(4):487-503. doi: 10.1002/(sici)1096-9861(19981102)400:4<487::aid-cne4>3.0.co;2-6.
Striatal tissue concentrations of neurotensin, expression of neurotensin/neuromedin N (NT/N) mRNA, and numbers of neurotensin-immunoreactive neurons are increased by d-amphetamine (amph), which stimulates dopamine release in the striatum, and haloperidol (hal), a dopamine receptor antagonist with high affinity for D2-like receptors. The possibility that the effects of these drugs involve distinct subpopulations of striatal neurons was addressed in this study, in which the relative numbers and distributions of striatal neuron profiles containing neurotensin immunoreactivity and/or NT/N mRNA were compared following administrations of hal, amph, hal and amph co-administered, and vehicle. Fourteen striatal subterritories in caudate-putamen, nucleus accumbens, and olfactory tubercle were evaluated. Amph produced increases in the expression of neurotensin preferentially in the ventromedial and caudodorsal subterritories of the caudate-putamen, the rostrobasal cell cluster and lateral shell of the nucleus accumbens, and the olfactory tubercle. Haloperidol produced increased neurotensin expression in much of dorsal and ventral striatum, most prominently in the rostral, dorsomedial and ventrolateral quadrants of the caudate-putamen, and in the rostrobasal cell cluster, rostral pole, medial and lateral shell of the nucleus accumbens and the olfactory tubercle. The numbers of neurons responding to amph and hal in all subterritories following co-administration of the two drugs were significantly less than the summed numbers responding individually to amph and hal. Furthermore, in the subterritories where immunohistochemically detectable responses elicited by amph exceeded those produced by hal, co-administration of the two drugs resulted in responses comparable to those elicited by hal given alone. It is suggested that some of the reported anti-dopaminergic behavioral effects of basal ganglia neurotensin may be attenuated in conditions of reduced dopamine neurotransmission.
d-苯丙胺（安非他明）可刺激纹状体中的多巴胺释放，氟哌啶醇是一种对D2样受体具有高亲和力的多巴胺受体拮抗剂，它们均可增加纹状体组织中神经降压素的浓度、神经降压素/神经介素N（NT/N）mRNA的表达以及神经降压素免疫反应性神经元的数量。本研究探讨了这些药物的作用是否涉及纹状体神经元的不同亚群，其中比较了在给予氟哌啶醇、安非他明、氟哌啶醇与安非他明联合给药以及赋形剂后，含有神经降压素免疫反应性和/或NT/N mRNA的纹状体神经元轮廓的相对数量和分布。对尾状核-壳核、伏隔核和嗅结节中的14个纹状体亚区域进行了评估。安非他明优先增加尾状核-壳核腹内侧和尾背侧亚区域、伏隔核吻基底细胞簇和外侧壳以及嗅结节中神经降压素的表达。氟哌啶醇使大部分背侧和腹侧纹状体中的神经降压素表达增加，最显著的是在尾状核-壳核的吻侧、背内侧和腹外侧象限，以及伏隔核的吻基底细胞簇、吻极、内侧和外侧壳以及嗅结节。两种药物联合给药后，所有亚区域中对安非他明和氟哌啶醇有反应的神经元数量显著少于单独对安非他明和氟哌啶醇有反应的神经元数量之和。此外，在免疫组织化学检测到的安非他明引起的反应超过氟哌啶醇引起的反应的亚区域中，可以观察到联合给药产生的反应与单独给予氟哌啶醇产生的反应相当。这表明在多巴胺神经传递减少的情况下，基底神经节神经降压素报告的一些抗多巴胺能行为效应可能会减弱。
