Moreau J L, Bourson A, Jenck F, Martin J R, Mortas P
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
J Psychiatry Neurosci. 1994 Jan;19(1):51-6.
This study was designed to validate a novel animal model of depression by testing the curative effects of the atypical antidepressant mianserin. In this paradigm, the hedonic state of rats was assessed using an intracranial self-stimulation (ICSS) procedure. The ICSS threshold was determined before, during and after a 38-day period of exposure to a variety of intermittent, unpredictable, mild stressors. After 11 days of this regimen, the ICSS threshold was significantly higher in the stressed rats, suggesting a gradual decrease of sensitivity to reward. This "anhedonia" lasted throughout the stress regimen and progressively diminished over a 20-day period after stress was terminated. When stressed animals exhibiting anhedonia were treated with mianserin, the stress-induced increase in the ICSS threshold was gradually reversed over ten days of treatment. These results provide further support for the value of this anhedonia paradigm in modelling an important aspect of human depressive disorders.
本研究旨在通过测试非典型抗抑郁药米安色林的疗效来验证一种新型抑郁症动物模型。在此范式中,使用颅内自我刺激(ICSS)程序评估大鼠的享乐状态。在暴露于各种间歇性、不可预测的轻度应激源的38天期间之前、期间和之后测定ICSS阈值。在该方案实施11天后,应激大鼠的ICSS阈值显著更高,表明对奖励的敏感性逐渐降低。这种“快感缺失”在整个应激方案期间持续存在,并在应激终止后的20天内逐渐减轻。当用米安色林治疗表现出快感缺失的应激动物时,应激诱导的ICSS阈值升高在治疗的十天内逐渐逆转。这些结果为这种快感缺失范式在模拟人类抑郁症重要方面的价值提供了进一步支持。