Moreau J L, Jenck F, Martin J R, Mortas P, Haefely W
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Pharmacopsychiatry. 1993 Jan;26(1):30-3. doi: 10.1055/s-2007-1014338.
This study was designed to investigate the predictive validity of a recently described chronic mild-stress-induced anhedonia model of depression. In an intracranial self-stimulation (ICSS) paradigm, rats were allowed to self-stimulate in the ventral tegmental area. Stimulation frequency thresholds for ICSS responses were determined prior to, during, and after a 19-day period of exposure to a variety of mild, intermittent, unpredictable stressors. After nine days of mild stress, stimulation threshold was significantly increased, suggesting a gradual decrease in the rewarding properties of brain stimulation. This anhedonic state lasted throughout the stress period and slowly disappeared over a 10-day period after termination of the stress regimen. This stress-induced increase in ICSS threshold was not observed in rats that were stressed and concomitantly treated with the reversible inhibitor of monoamine oxidase type A (RIMA) moclobemide (20 mg/kg, b.i.d.). In nonstressed animals treated with vehicle or moclobemide, no significant change in ICSS occurred during the course of the experiment. These experimental results reinforce the value of this animal model with respect to its predictive and construct validity.
本研究旨在探讨最近描述的慢性轻度应激诱导的抑郁症快感缺失模型的预测效度。在颅内自我刺激（ICSS）范式中，大鼠被允许在腹侧被盖区进行自我刺激。在暴露于各种轻度、间歇性、不可预测应激源的19天期间之前、期间和之后，确定ICSS反应的刺激频率阈值。轻度应激九天后，刺激阈值显著增加，表明脑刺激的奖赏特性逐渐降低。这种快感缺失状态在整个应激期间持续存在，并在应激方案终止后的10天内缓慢消失。在接受应激并同时用A型单胺氧化酶可逆抑制剂（RIMA）吗氯贝胺（20mg/kg，每日两次）治疗的大鼠中未观察到这种应激诱导的ICSS阈值增加。在用赋形剂或吗氯贝胺治疗的非应激动物中，实验过程中ICSS未发生显著变化。这些实验结果强化了该动物模型在预测效度和结构效度方面的价值。
