Kilts C D, Anderson C M, Bissette G, Ely T D, Nemeroff C B
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Biochem Pharmacol. 1988 Apr 15;37(8):1547-54. doi: 10.1016/0006-2952(88)90017-2.
The present study mapped the topographic distribution of, and the effect of neuropharmacologically distinct antipsychotic drugs on, the concentration of neurotensin (NT) in the rat brain at the level of discrete nuclei or areas. The chronic administration of either haloperidol or clozapine increased the concentration of NT-like immunoreactivity (NT-LI) in the nucleus accumbens and decreased it in the medial prefrontal and cingulate cortex and in the interstitial (bed) nucleus of the stria terminalis. In contrast, the prolonged administration of haloperidol, but not clozapine, increased the concentration of NT-LI in the anterior caudate nucleus and posterior caudate-putamen. The concentration of NT-LI in the great majority of the rat brain nuclei examined was unaffected by the chronic administration of either antipsychotic drug. This pattern of pharmacological response distinguishes NT from all other neuropeptides which have been shown to be influenced by prolonged antipsychotic drug administration. These findings suggest that the functional information imparted to NT-containing cells by neuronal dopamine (DA) release, as inferred from the consequences of receptor blockade, varies remarkably between different populations of DA neurons and further implicate NT as a neuroanatomically-selective neurochemical substrate of the adaptive responses mediating the therapeutic and motoric side effects of antipsychotic drugs.
本研究绘制了大鼠脑内离散核团或区域水平上神经降压素（NT）浓度的拓扑分布图，以及神经药理学特性不同的抗精神病药物对其的影响。长期给予氟哌啶醇或氯氮平，会使伏隔核中NT样免疫反应性（NT-LI）浓度升高，而使内侧前额叶皮质、扣带回皮质以及终纹床核中的NT-LI浓度降低。相比之下，长期给予氟哌啶醇（而非氯氮平）会使尾状核前部和尾壳核后部的NT-LI浓度升高。所检测的大鼠脑内绝大多数核团中的NT-LI浓度不受这两种抗精神病药物长期给药的影响。这种药理反应模式将NT与所有其他已被证明受长期抗精神病药物给药影响的神经肽区分开来。这些发现表明，从受体阻断的后果推断，神经元多巴胺（DA）释放赋予含NT细胞的功能信息在不同的DA神经元群体之间存在显著差异，这进一步表明NT是介导抗精神病药物治疗和运动副作用的适应性反应的神经解剖学选择性神经化学底物。
