Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone
Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone
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DOI：
10.1111/j.1471-4159.2009.06168.x
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发表时间：
2009-07-01
影响因子：
4.7
通讯作者：
Baba, Akemichi
中科院分区：
文献类型：
--
作者：
Hashimoto, Hitoshi;Hashimoto, Ryota;Baba, Akemichi
腺苷酸环化酶激活多肽（PACAP）是一种具有多效性功能的神经肽。我们在这里报告，PACAP缺陷（PACAP-/-）小鼠表现出增加不动性在强迫游泳试验中，这是减少了抗抑郁药地昔帕明，在野生型小鼠相似的程度。非典型抗精神病药利培酮和选择性5-羟色胺（5-HT）（2）拮抗剂利坦色林使PACAP-/-小鼠的抑郁样行为正常化。5-HT 2激动剂（+/-）-2，5-二甲氧基-4-碘苯丙胺诱导的5-HT综合征在PACAP-/-小鼠中被夸大，这表明抑郁样行为中的5-HT 2受体依赖性机制。血浆皮质酮和身体核心温度的昼夜节律显着平坦的突变体。在突变的海马中糖皮质激素受体的mRNA表达减少。目前的研究结果表明，PACAP信号的改变可能有助于某些抑郁症的发病机制，适合非典型抗精神病药物。
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic functions. We report here that PACAP-deficient (PACAP-/-) mice showed increased immobility in a forced swimming test, which was reduced by the antidepressant desipramine, to a similar extent as in wild-type mice. The atypical antipsychotic risperidone and the selective serotonin (5-HT)(2) antagonist ritanserin normalized the depression-like behavior in PACAP-/- mice. The 5-HT2 agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine-induced 5-HT syndrome was exaggerated in PACAP-/- mice, which suggests a 5-HT2-receptor-dependent mechanism in the depression-like behavior. The circadian rhythm of plasma corticosterone and body core temperature was significantly flattened in the mutants. mRNA expression of glucocorticoid receptor was reduced in the mutant hippocampus. The present results suggest that alterations in PACAP signaling might contribute to the pathogenesis of certain depressive conditions amenable to atypical antipsychotic drugs.