Iijima Michihiko, Chaki Shigeyuki
Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Kita-ku, Saitama, Japan.
Pharmacol Biochem Behav. 2005 Dec;82(4):652-7. doi: 10.1016/j.pbb.2005.11.005. Epub 2005 Dec 15.
In rat pups, ultrasonic vocalizations were emitted in response to separation from the mothers, littermates, and nest. It has been suggested that these separation-induced ultrasonic vocalizations (SIV) in rat pups form one of the animal models of anxiety. The primary aim of the present study is to investigate the effect of the compounds acting on stress-related peptide receptors such as a vasopressin V1b receptor antagonist and a corticotropin-releasing factor CRF1 receptor antagonist in rat pup SIV. The secondary objective is to establish further confirmation of the predictive validity of SIV testing. Both the V1b receptor antagonist SSR149415 and the CRF1 receptor antagonist CP154,526 reduced SIV, suggesting antagonists for stress-related peptide receptors are effective in this model. Furthermore, as with selective serotonin reuptake inhibitors such as fluvoxamine and paroxetine, SIV was also reduced by the serotonin and noradrenaline reuptake inhibitor milnacipran and the metabotropic glutamate receptor 5 antagonist MPEP, while desipramine was without effect. Thus, the present experiment highlights the important role of the stress-related peptide systems as well as of the serotonergic systems in SIV. Moreover, the present data support the usefulness of SIV for evaluating the anxiolytic-like activity of mechanically diverse compounds.
在幼鼠中，超声发声是对与母亲、同窝幼崽和巢穴分离的反应。有人提出，幼鼠中这些分离诱导的超声发声（SIV）构成了焦虑的动物模型之一。本研究的主要目的是研究作用于应激相关肽受体的化合物，如血管加压素V1b受体拮抗剂和促肾上腺皮质激素释放因子CRF1受体拮抗剂对幼鼠SIV的影响。次要目的是进一步确认SIV测试的预测有效性。V1b受体拮抗剂SSR149415和CRF1受体拮抗剂CP154,526均降低了SIV，表明应激相关肽受体拮抗剂在该模型中有效。此外，与氟伏沙明和帕罗西汀等选择性5-羟色胺再摄取抑制剂一样，5-羟色胺和去甲肾上腺素再摄取抑制剂米那普明和代谢型谷氨酸受体5拮抗剂MPEP也降低了SIV，而地昔帕明则无作用。因此，本实验突出了应激相关肽系统以及5-羟色胺能系统在SIV中的重要作用。此外，本数据支持SIV在评估结构多样的化合物的抗焦虑样活性方面的有用性。
