Do-Rego Jean-Claude, Chatenet David, Orta Marie-Hélène, Naudin Bertrand, Le Cudennec Camille, Leprince Jérôme, Scalbert Elizabeth, Vaudry Hubert, Costentin Jean
Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Laboratoire de Neuropsychopharmacologie Experimentale, CNRS FRE 2735, UFR de Medecine et Pharmacie, 76183 Rouen Cedex, France.
Psychopharmacology (Berl). 2005 Nov;183(1):103-17. doi: 10.1007/s00213-005-0140-2. Epub 2005 Oct 22.
Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.
尾加压素II(U-II)受体广泛分布于中枢神经系统。脑室内(i.c.v.)注射U-II会导致高血压和心动过缓,并刺激催乳素和促甲状腺激素分泌。然而,中枢给予U-II的行为效应很少受到关注。在本研究中,我们测试了脑室内注射U-II对小鼠行为、代谢和内分泌反应的影响。给予不同剂量的U-II(1-10,000 ng/小鼠)会引发:(1)在洞板试验中,头部探入次数呈剂量依赖性减少;(2)在黑白隔室试验中,白色隔室进入次数呈剂量依赖性减少,在十字迷宫试验中,中央平台和开放臂进入次数呈剂量依赖性减少;(3)在强迫游泳试验和悬尾试验中,不动时间呈剂量依赖性增加。脑室内注射U-II还会导致:剂量为100和1,000 ng/小鼠时食物摄入量增加,剂量为100-10,000 ng/小鼠时饮水量增加,剂量为10,000 ng/小鼠时水平运动活动增加。无论剂量如何,中枢给予U-II对体温、痛觉、阿扑吗啡诱导的阴茎勃起和攀爬行为以及应激诱导的血浆皮质酮水平均无影响。综上所述,本研究表明,以1-10,000 ng/小鼠的剂量脑室内注射U-II会在小鼠中诱导出焦虑样和抑郁样效应。这些数据表明,U-II可能参与了精神疾病的某些方面。