Uhl G R, Kuhar M J
Nature. 1984;309(5966):350-2. doi: 10.1038/309350a0.
Antischizophrenic neuroleptic drugs interact with brain dopamine systems in producing both therapeutic and unwanted side effects. Short-term administration of neuroleptics may produce a parkinsonian, hypokinetic syndrome mimicking symptoms of dopamine depletion, and presumably caused by dopamine receptor blockade. Paradoxically, some 20% of patients treated chronically with these agents develop tardive dyskinesia. The adventitious movements typical of this condition mimic symptoms of dopamine excess despite continuing receptor blockade. Dopamine receptor supersensitivity does develop in such conditions, but its extent does not correlate well with the presence or absence of tardive dyskinesia. Exploration of neuroleptic-induced alterations in other dopamine-associated systems may thus provide insight into these processes. Dopamine-containing cells of the substantia nigra, prominently implicated in the motor side effects of neuroleptics, possess dense concentrations of receptors for the putative peptide neurotransmitter, neurotensin. Here we report that these receptors are substantially increased in both rats and humans after chronic treatment with neuroleptic drugs, and discuss possible implications of this finding for our understanding of neuroleptic actions.
抗精神分裂症的神经安定药物在产生治疗作用和不良副作用时都会与脑内多巴胺系统相互作用。短期使用神经安定药物可能会产生一种类似帕金森病的运动减少综合征，类似于多巴胺耗竭的症状，推测是由多巴胺受体阻断引起的。矛盾的是，约20%长期使用这些药物治疗的患者会出现迟发性运动障碍。尽管受体持续被阻断，但这种疾病典型的不自主运动却类似于多巴胺过量的症状。在这种情况下确实会发生多巴胺受体超敏，但超敏程度与迟发性运动障碍的有无并没有很好的相关性。因此，探索神经安定药物引起的其他多巴胺相关系统的变化可能有助于深入了解这些过程。黑质中含多巴胺的细胞在神经安定药物的运动副作用中起主要作用，这些细胞拥有高浓度的一种假定的肽类神经递质——神经降压素的受体。我们在此报告，经神经安定药物长期治疗后，大鼠和人类体内的这些受体都显著增加，并讨论了这一发现对于我们理解神经安定药物作用的可能意义。
