Fuchs E, Kramer M, Hermes B, Netter P, Hiemke C
Division of Neurobiology, German Primate Center, Göttingen, Germany.
Pharmacol Biochem Behav. 1996 May;54(1):219-28. doi: 10.1016/0091-3057(95)02166-3.
Male tree shrews (Tupaia belangeri) provide an animal model to study the neurobehavioral consequences of chronic psychosocial stress. When living in visual and olfactory contact with a male conspecific by which it has been defeated, the subordinante tree shrew shows dramatic behavioral, physiological, and neuroendocrine changes. Because the over all pattern of these changes resemble a depression-like symptomatology, we investigated to what extent the behavioral and endocrine changes in subordinate animals can be reversed by treatment with the tricyclic antidepressant clomipramine. In the present study, animals were subjected to a 10-day period of psychosocial conflict to elicit stress-induced behavioral and endocrine alterations before the onset of drug treatment, and psychosocial stress continued throughout the treatment period of 30 days. Clomipramine was administered orally once daily at a dose of 50 mg/kg. The drug had a time-dependent restorative influence on marking and grooming behavior, locomotor activity, risk assessment, as well as on urinary cortisol and norepinephrine excretion. It, thus, appears that the clomipramine treatment counteracts the behavioral and endocrine effects of chronic psychosocial stress in tree shrews, and the time course of recovery corresponds closely to that observed when treating depressed patients in the clinic.
雄性树鼩(笔尾树鼩)为研究慢性心理社会应激的神经行为后果提供了一种动物模型。当与一只战胜过自己的雄性同种个体处于视觉和嗅觉可接触的环境中时,从属树鼩会表现出显著的行为、生理和神经内分泌变化。由于这些变化的总体模式类似于抑郁样症状,我们研究了用三环类抗抑郁药氯米帕明治疗能在多大程度上逆转从属动物的行为和内分泌变化。在本研究中,在药物治疗开始前,让动物经历为期10天的心理社会冲突,以引发应激诱导的行为和内分泌改变,并且在整个30天的治疗期内持续施加心理社会应激。氯米帕明以50mg/kg的剂量每日口服一次。该药物对标记和梳理行为、运动活动、风险评估以及尿皮质醇和去甲肾上腺素排泄具有时间依赖性的恢复作用。因此,氯米帕明治疗似乎抵消了树鼩慢性心理社会应激的行为和内分泌影响,并且恢复的时间进程与临床上治疗抑郁症患者时观察到的情况密切对应。