Antidepressant-like effects of the delta-opioid receptor agonist SNC80 ([(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide) in an olfactory bulbectomized rat model
Antidepressant-like effects of the delta-opioid receptor agonist SNC80 ([(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenzamide) in an olfactory bulbectomized rat model
复制标题
δ-阿片受体激动剂 SNC80 ([( )-4-[(alphaR)-alpha-[(2S,5R)-2,5-二甲基-4-(2-丙烯基)-1-哌嗪基] 的抗抑郁样作用
DOI：
10.1016/j.brainres.2007.07.095
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发表时间：
2008
期刊：
影响因子：
2.9
通讯作者：
J. Kamei
中科院分区：
文献类型：
--
作者：
A. Saitoh;M. Yamada;M. Yamada;Kou Takahashi;K. Yamaguchi;H. Murasawa;Akiko Nakatani;Yoshimi Tatsumi;Noritaka Hirose;J. Kamei
嗅球切除（OBX）大鼠的抗抑郁治疗的反应是类似的抑郁症患者，因为长期服用抗抑郁药逆转OBX诱导的行为和生理变化。以前，使用几种动物模型，证明了用δ-阿片受体激动剂单次治疗产生抗抑郁样作用。本研究在OBX大鼠抑郁模型中检查了δ阿片受体激动剂SNC 80亚慢性暴露8天所产生的抗抑郁作用。通过抽吸去除嗅球。通过对大鼠对给定刺激的反应进行评分来测量大鼠的情绪，即，攻击惊吓挣扎和打斗反应在手术后第14天用载体长期处理7天的OBX大鼠显示情绪性评分显著增加，并且在十字迷宫的开放臂中花费的时间和进入次数减少。在OBX大鼠的情况下，这些变化通过慢性SNC 80治疗（1-10 mg/kg，s.c.）腹腔注射地昔帕明10 mg/kg，连续7 d。此外，5-HT及其代谢产物5-HIAA在额叶皮质，海马和杏仁核的浓度降低OBX大鼠，这些变化也正常化SNC 80治疗，而不是地昔帕明治疗。此外，SNC 80还显著逆转了由OBX产生的中缝背核TH阳性细胞的丢失。总之，我们证明了亚慢性SNC 80治疗可以完全逆转OBX诱导的行为异常和多巴胺能功能缺陷。
The responses of olfactory bulbectomized (OBX) rats to antidepressant treatment are similar to those of depressed patients since chronic administration of an antidepressant reverses OBX-induced behavioral and physiological changes. Previously, using several animal models, it was demonstrated that single treatment with delta-opioid receptor agonists produced an antidepressant-like effect. This study examined the antidepressant effects resulting from subchronic exposure for 8 days to the delta-opioid receptor agonist SNC80 in an OBX rat model of depression. The olfactory bulbs were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed a significant increase in emotionality score and a decrease in the time spent and entries in the open arm of a plus-maze. In the case of OBX rats, these changes were dose- and time-dependently reversed by chronic SNC80 treatment (1–10 mg/kg, s.c.) for 7 days, as same as desipramine (10 mg/kg, i.p.). Moreover, the concentration of 5-HT and its metabolite 5-HIAA in the frontal cortex, hippocampus, and amygdala were decreased in OBX rats, and these changes were also normalized by SNC80 treatment, rather than desipramine treatment. In addition, SNC80 also significantly reversed the loss of TH-positive cells produced by OBX in the dorsal raphe. In conclusion, we demonstrated that subchronic SNC80 treatment could completely reverse OBX-induced behavioral abnormalities and defects in serotonergic function.