Hertel P, Fagerquist M V, Svensson T H
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden.
Science. 1999 Oct 1;286(5437):105-7. doi: 10.1126/science.286.5437.105.
Clozapine exerts superior clinical efficacy and markedly enhances cortical dopamine output compared with classical antipsychotic drugs. Here the alpha2 adrenoceptor antagonist idazoxan was administered to rats alone or in combination with the D2/3 dopamine receptor antagonist raclopride. Dopamine efflux in the medial prefrontal cortex and conditioned avoidance responding were analyzed. Idazoxan selectively potentiated the cortical output of dopamine and augmented the suppression of conditioned avoidance responding induced by raclopride. These results challenge basic assumptions underlying the dopamine hypothesis of schizophrenia and provide insight into clozapine's mode of action.
与经典抗精神病药物相比，氯氮平具有更高的临床疗效，并且能显著提高皮质多巴胺的释放量。在此研究中，单独或联合D2/3多巴胺受体拮抗剂雷氯必利给大鼠注射α2肾上腺素能受体拮抗剂伊达唑胺。分析内侧前额叶皮质中的多巴胺外流和条件性回避反应。伊达唑胺选择性地增强了多巴胺的皮质释放，并增强了雷氯必利诱导的条件性回避反应的抑制作用。这些结果对精神分裂症多巴胺假说的基本假设提出了挑战，并为氯氮平的作用模式提供了深入见解。
