Duval Fabrice, Mokrani Marie-Claude, Erb Alexis, Gonzalez Lopera Felix, Danila Vlad, Tomsa Mihaela
Pôle 8/9-APF2R, Centre Hospitalier, 68250 Rouffach, France.
Brain Sci. 2021 Mar 26;11(4):425. doi: 10.3390/brainsci11040425.
The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic-hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic-pituitary-adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.
抗抑郁药对中脑边缘 - 下丘脑系统中多巴胺（DA）受体敏感性的影响产生了相互矛盾的结果。通过对16名未服用药物的符合《精神疾病诊断与统计手册》第5版（DSM - 5）标准的重度抑郁住院患者和18名健康住院对照（HC）受试者给予阿扑吗啡（APO；0.75 mg皮下注射）后皮质醇的反应，评估突触后DA受体功能。还测量了地塞米松抑制试验（DST）的皮质醇反应。在抗抑郁治疗（ADT）两周和四周后，对所有患者重复进行DST和APO试验。如通过DST评估的那样，对APO的皮质醇反应（∆COR）不受下丘脑 - 垂体 - 肾上腺（HPA）轴活性的影响。患者和HCs治疗前的∆COR值无显著差异。在ADT期间，第2周和第4周时患者的∆COR值低于HCs。治疗四周后，在∆COR值降低的8名患者中，7名随后缓解，而在∆COR值正常的8名患者中，7名未缓解。考虑到我们研究的局限性，结果表明，长期ADT后，下丘脑水平与HPA轴调节相关的突触后DA受体脱敏与临床缓解有关。这些结果可能反映了中脑边缘通路中DA水平的升高。
