Shimazaki Toshiharu, Iijima Michihiko, Chaki Shigeyuki
Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Eur J Pharmacol. 2006 Aug 14;543(1-3):63-7. doi: 10.1016/j.ejphar.2006.06.032. Epub 2006 Jun 27.
A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.
血管加压素V(1B)受体拮抗剂已被证明在多种焦虑动物模型中具有抗焦虑作用。在本研究中,我们通过在大鼠中进行社交互动试验,研究了垂体在血管加压素V(1B)受体拮抗剂抗焦虑作用中的参与情况。在假手术大鼠中,血管加压素V(1B)受体拮抗剂SSR149415和苯二氮䓬类药物氯氮卓均显著增加了一对陌生大鼠的社交行为,并且在社交互动试验期间血促肾上腺皮质激素水平显著升高。垂体切除也使动物进行社交行为的时间长度增加,增加程度与假手术大鼠用抗焦虑药治疗后观察到的相同。然而,虽然氯氮卓进一步增加了垂体切除大鼠的社交互动持续时间,但在这些动物中不再观察到SSR149415的抗焦虑作用。这些结果表明,血管加压素V(1B)受体拮抗剂在社交互动试验中的抗焦虑作用是通过阻断垂体中的血管加压素V(1B)受体介导的。