Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Kraków, Poland.
Institute of Pharmacology, Polish Academy of Sciences, Department of Pharmacology, Kraków, Poland.
Pharmacol Rep. 2018 Oct;70(5):1023-1031. doi: 10.1016/j.pharep.2018.04.009. Epub 2018 May 1.
Preclinical and clinical studies have suggested a beneficial effect of combination treatment with atypical antipsychotic drugs and antidepressants (ADs) in schizophrenia and in drug-resistant depression.
In the present study, we investigated the effect of chronic administration of risperidone and ADs (escitalopram or mirtazapine), given separately or jointly on the extracellular levels of dopamine (DA) and serotonin (5-HT) in the rat frontal cortex. The animals were administered risperidone (0.2mg/kg) and escitalopram (5mg/kg) or mirtazapine (10mg/kg) repeatedly for 14days. The release of monoamines in the rat frontal cortex was evaluated using a microdialysis, and DA and 5-HT levels were assayed by HPLC. We also measured the locomotor activity, catalepsy and recognition memory in these rats.
Chronic risperidone treatment (0.2mg/kg) increased the extracellular levels of DA and 5-HT. Co-treatment with risperidone and escitalopram (5mg/kg) or mirtazapine (10mg/kg) more efficiently increased the release of 5-HT but not DA in the rat frontal cortex, as compared to drugs given alone. Moreover, risperidone, escitalopram and mirtazapine given alone or in combination significantly decreased the locomotor activity and only mirtazapine increased the catalepsy evoked by risperidone. Combined treatment with risperidone and ADs impaired recognition memory in these rats.
The obtained results suggest that chronic co-administration of risperidone and escitalopram or mirtazapine more efficiently increased 5-HT release in the rat frontal cortex as compared to drugs given alone and suggest that this effect may be of importance to the pharmacotherapy of schizophrenia and drug-resistant depression.
临床前和临床研究表明，在精神分裂症和耐药性抑郁症中，联合使用非典型抗精神病药物和抗抑郁药（ADs）进行治疗具有有益的效果。
在本研究中，我们研究了利培酮和 ADs（依地普仑或米氮平）的慢性给药，分别或联合给药对大鼠前额皮质中外源多巴胺（DA）和 5-羟色胺（5-HT）水平的影响。这些动物反复接受利培酮（0.2mg/kg）和依地普仑（5mg/kg）或米氮平（10mg/kg）治疗 14 天。使用微透析评估大鼠前额皮质中单胺的释放，并用 HPLC 测定 DA 和 5-HT 水平。我们还测量了这些大鼠的运动活动、僵住症和识别记忆。
慢性利培酮治疗（0.2mg/kg）增加了 DA 和 5-HT 的细胞外水平。与单独给药相比，利培酮与依地普仑（5mg/kg）或米氮平（10mg/kg）联合治疗更有效地增加了大鼠前额皮质中 5-HT 的释放，但不会增加 DA 的释放。此外，利培酮、依地普仑和米氮平单独或联合给药均显著降低了运动活动，只有米氮平增加了利培酮引起的僵住症。联合使用利培酮和 ADs 损害了这些大鼠的识别记忆。
研究结果表明，与单独给药相比，慢性联合使用利培酮和依地普仑或米氮平更有效地增加了大鼠前额皮质中 5-HT 的释放，这表明这种作用可能对精神分裂症和耐药性抑郁症的药物治疗具有重要意义。
