Ossowska G, Nowa G, Kata R, Klenk-Majewska B, Danilczuk Z, Zebrowska-Lupina I
Department of Clinical Pharmacology. Medical University School, Lublin, Poland.
J Neural Transm (Vienna). 2001;108(3):311-9. doi: 10.1007/s007020170077.
Antidepressant drugs are devoid of mood-elevating effects in normal (non-depressed) human subjects, thus, it is necessary to evaluate the antidepressant property of compounds (drugs) in animal models of depression. Several animal models of depression have been introduced, however, only a few have been extensively validated. In the present study we report the results of investigations into monoaminergic receptors in the brain of rats subjected to chronic unpredictable stress (CUS) procedure (one of the well validated animal models of depression). We have examined the dopaminergic (D-1, D-2), adrenergic (alpha-1, beta-1) and serotonergic (5HT-1A, 5HT-2A) receptors in different brain regions by a saturation radioligand binding method in rats subjected to CUS paradigm and control animals. CUS procedure resulted in a significant 29% increase in the D-1 receptor density in the limbic system and 52% increase of the density of 5HT-2A receptors in the cerebral cortex. The present data indicate that the increase of the density of brain D-1 and 5HT-2A receptors of rats subjected to CUS might be involved in the pathophysiology of "animal depression" (since chronic antidepressant treatment produced opposite changes i.e. decrease in the density of these receptors) and thus in pathophysiology of human depression.
抗抑郁药物对正常(非抑郁)人类受试者没有情绪提升作用,因此,有必要在抑郁症动物模型中评估化合物(药物)的抗抑郁特性。已经引入了几种抑郁症动物模型,然而,只有少数模型得到了广泛验证。在本研究中,我们报告了对经历慢性不可预测应激(CUS)程序(一种经过充分验证的抑郁症动物模型)的大鼠大脑中单胺能受体的研究结果。我们通过饱和放射性配体结合法,在接受CUS范式的大鼠和对照动物的不同脑区中检测了多巴胺能(D-1、D-2)、肾上腺素能(α-1、β-1)和5-羟色胺能(5HT-1A、5HT-2A)受体。CUS程序导致边缘系统中D-1受体密度显著增加29%,大脑皮层中5HT-2A受体密度增加52%。目前的数据表明,经历CUS的大鼠大脑中D-1和5HT-2A受体密度的增加可能与“动物抑郁”的病理生理学有关(因为长期抗抑郁治疗产生了相反的变化,即这些受体密度降低),从而也与人类抑郁症的病理生理学有关。