Van Kampen M, Schmitt U, Hiemke C, Fuchs E
Division of Neurobiology, German Primate Centre, 37077, Göttingen, Germany.
Pharmacol Biochem Behav. 2000 Mar;65(3):539-46. doi: 10.1016/s0091-3057(99)00190-2.
The present study evaluated the effect of subchronic oral treatment of psychosocially stressed male tree shrews with diazepam on locomotor activity, marking behavior, avoidance behavior, and urinary cortisol and noradrenaline. To mimic a realistic situation of anxiolytic intervention, the treatment started 14 days after the beginning of psychosocial stress; at that time, the stress-induced behavioral and endocrine alterations had been established. The drug (5 mg/kg/day) was administered orally in the morning, while the psychosocial stress continued during the whole treatment period; the therapeutic action of diazepam treatment was followed across 7 days. Twenty-four hours after the last application serum concentrations of diazepam and its major metabolites were determined via HPLC. The results revealed concentrations of 7 ng/ml for diazepam, 106 ng/ml for nordiazepam, 22 ng/ml for temazepam, and 30 ng/ml for oxazepam. Treatment of subordinate animals with diazepam did not reveal a beneficial effect to any of the parameters studied. This contrasts to earlier findings showing that the behavioral and neuroendocrine alterations produced by this stress paradigm are sensitive to chronic treatment with the tricyclic antidepressant clomipramine. The present results support the view that in male tree shrews the state induced by psychosocial stress might be more depression related than anxiety related.
本研究评估了对遭受心理社会应激的雄性树鼩进行为期亚慢性口服地西泮治疗，对其运动活动、标记行为、回避行为以及尿皮质醇和去甲肾上腺素的影响。为模拟抗焦虑干预的实际情况，在心理社会应激开始14天后开始治疗；此时，应激诱导的行为和内分泌改变已经形成。药物（5毫克/千克/天）于早晨口服，而心理社会应激在整个治疗期间持续存在；对地西泮治疗的疗效进行了7天的跟踪观察。在最后一次给药24小时后，通过高效液相色谱法测定血清中地西泮及其主要代谢产物的浓度。结果显示地西泮浓度为7纳克/毫升，去甲地西泮为106纳克/毫升，替马西泮为22纳克/毫升，奥沙西泮为30纳克/毫升。用地西泮治疗从属动物对所研究的任何参数均未显示有益效果。这与早期研究结果形成对比，早期研究表明这种应激模式所产生的行为和神经内分泌改变对三环类抗抑郁药氯米帕明的慢性治疗敏感。目前的结果支持这样一种观点，即在雄性树鼩中，心理社会应激所诱发的状态可能与抑郁的关系比与焦虑的关系更大。
