According to preclinical and clinical studies, the antidepressant-induced increase in the activity of atypical antipsychotics may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. In the present study, we aimed to evaluate the effects of the antidepressants escitalopram and mirtazapine and the atypical antipsychotic drug aripiprazole, administered separately or in combination, on the MK-801-induced deficits in the recognition memory test and on the extracellular levels of monoamines and their metabolites in the rat frontal cortex.

Based on the results of the behavioral tests, co-treatment with an ineffective dose of aripiprazole (0.1 mg/kg) and escitalopram (2.5 and 5 mg/kg) or mirtazapine (5 mg/kg) abolished the deficits evoked by MK-801 in the novel object recognition test, and those effects were blocked by the 5-HT_1A receptor antagonist (WAY 100,635) or the dopamine D₁ receptor antagonist (SCH 23,390). Moreover, co-treatment with aripiprazole (0.3 mg/kg) and escitalopram (5 mg/kg) significantly increased the levels of noradrenaline and serotonin, decreased the level of its metabolite, and did not alter level of dopamine, but decreased the levels of its metabolites. In addition, co-treatment with aripiprazole (0.3 mg/kg) and mirtazapine (10 mg/kg) significantly increased the level of noradrenaline, did not change the levels of dopamine and serotonin, but increased the levels of their metabolites. Based on these results, the increase in the extracellular levels of noradrenaline or serotonin in the cortex induced by co-treatment with an antidepressant and aripiprazole may be very important for the pharmacotherapy of negative and some cognitive symptoms of schizophrenia.

根据临床前和临床研究，抗抑郁药诱导的非典型抗精神病药活性增加可能有效改善精神分裂症的阴性症状和某些认知症状的治疗。在本研究中，我们旨在评估抗抑郁药依他普仑和米氮平以及非典型抗精神病药物阿立哌唑单独或联合给药对 MK-801 诱导的识别记忆测试缺陷和细胞外单胺水平的影响及其在大鼠额叶皮层中的代谢物。

根据行为测试的结果，与无效剂量的阿立哌唑 (0.1 mg/kg) 和依他普仑 (2.5 和 5 mg/kg) 或米氮平 (5 mg/kg) 共同治疗消除了 MK-801 引起的缺陷在新的物体识别测试中，这些影响被 5-HT _1A受体拮抗剂 (WAY 100,635) 或多巴胺 D ₁阻断受体拮抗剂（SCH 23,390）。此外，与阿立哌唑 (0.3 mg/kg) 和依他普仑 (5 mg/kg) 联合治疗显着增加去甲肾上腺素和 5-羟色胺的水平，降低其代谢物的水平，并没有改变多巴胺的水平，但降低了其代谢产物。此外，阿立哌唑 (0.3 mg/kg) 和米氮平 (10 mg/kg) 的联合治疗显着增加了去甲肾上腺素的水平，没有改变多巴胺和血清素的水平，但增加了其代谢物的水平。基于这些结果，由抗抑郁药和阿立哌唑共同治疗引起的皮质中去甲肾上腺素或血清素的细胞外水平的增加对于精神分裂症的阴性和一些认知症状的药物治疗可能非常重要。