Department of Legal Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
J Toxicol Sci. 2011 Jan;36(1):31-41. doi: 10.2131/jts.36.31.
Anhedonia, an affective symptom related to the inability to experience pleasure, is one of the representative symptoms observed in depression. In the present study, considering that repeated nicotine (NC) also causes "depressive" symptoms, the depression-related anhedonic behavioral alterations caused by a typical depression-inducing stressor, immobilization stress (IM), combined with or without NC administration, were examined in mice and compared with the depression-like behavioral alterations caused by NC. In the repeated IM (10 min, 4 days) group, as well as the repeated NC (0.3 mg/kg, s.c., 4 days) group, depression-related behavioral despair was observed in both forced swimming and tail suspension tests. Depression-related anhedonic behavioral alterations, as judged in the sucrose test, were observed only in the IM group. In the group treated with IM plus NC (IM-NC group), NC antagonized the IM-induced anhedonic attenuation of sucrose consumption in the sucrose test. Furthermore, in the IM-NC group, NC attenuated the effects of antidepressants which inhibit the reuptake of monoamines in the forced swimming test. Against the IM-induced anhedonia in the sucrose test, the cannabinoid agonists anandamide and CP 55940, in addition to the antidepressants previously reported, restored the preference for sucrose to control levels, with or without NC co-treatment. The absence of anhedonic behavioral alterations, the antidepressant-like anti-anhedonic effects against IM, and the effects against some antidepressant drugs all seemed to be characteristic of the effects of NC. Neural mechanisms other than those involved in the depression-like effects of NC seemed to contribute to the IM-induced anhedonic component of depression.
快感缺失，一种与无法体验愉悦相关的情感症状，是抑郁症的代表性症状之一。在本研究中，考虑到重复尼古丁（NC）也会引起“抑郁”症状，因此检查了由典型的诱导抑郁应激源，束缚应激（IM）与或不与 NC 给药相结合引起的与抑郁相关的快感缺失行为改变，并与 NC 引起的类似抑郁的行为改变进行了比较。在重复 IM（10 分钟，4 天）组和重复 NC（0.3mg/kg，sc，4 天）组中，在强迫游泳和悬尾试验中均观察到与抑郁相关的行为绝望。在蔗糖试验中观察到与抑郁相关的快感缺失行为改变仅在 IM 组中。在 IM+NC 处理组（IM-NC 组）中，NC 拮抗了 IM 引起的蔗糖消耗快感缺失的衰减。此外，在 IM-NC 组中，NC 减弱了抑制单胺再摄取的抗抑郁药在强迫游泳试验中的作用。针对 IM 引起的蔗糖测试中的快感缺失，除了先前报道的抗抑郁药外，大麻素激动剂 anandamide 和 CP 55940 还恢复了对蔗糖的偏好，与 NC 共同处理或不处理。在蔗糖测试中没有快感缺失行为改变、对 IM 的抗抑郁抗快感缺失作用以及对某些抗抑郁药的作用，这些似乎都是 NC 作用的特征。除了与 NC 的类似抑郁作用相关的神经机制外，其他神经机制似乎也参与了 IM 诱导的抑郁快感缺失成分。
