Tatarczyńska E, Kłodzińska A, Stachowicz K, Chojnacka-Wójcik E
Institute of Pharmacology, Polish Academy of Sciences, 12 Smêtna Street, 31-343 Kraków, Poland.
Behav Pharmacol. 2004 Dec;15(8):523-34. doi: 10.1097/00008877-200412000-00001.
The purpose of the present study was to investigate the effects of the selective 5-HT1B receptor agonist CP 94253, the selective 5-HT1B receptor antagonist SB 216641, and the 5-HT1B/1D receptor antagonist GR 127935 in behavioral tests commonly used to predict anxiolytic- and antidepressant-like activity. Diazepam and imipramine were used as reference drugs. In the Vogel conflict drinking test, CP 94253 (1.25-5 mg/kg), SB 216641 (2.5-5 mg/kg) and GR 127935 (5-10 mg/kg) showed anxiolytic-like effects comparable to that of diazepam (2.5-5 mg/kg). In the elevated plus-maze test, antianxiety-like activity of all the compounds tested was also observed: the effects of CP 94253 (2.5 mg/kg) and SB 216641 (5 mg/kg) were similar to that of diazepam (5 mg/kg), while GR 127935 (up to 40 mg/kg) was less active. In the four-plate test, the compounds tested (5-10 mg/kg) produced anxiolytic-like effects which were weaker than that of diazepam (2.5-5 mg/kg). In the forced swimming test, CP 94253 (5-10 mg/kg), like imipramine (30 mg/kg), showed anti-immobility action, whereas SB 216641 (2.5-10 mg/kg) and GR 127935 (20-40 mg/kg) did not affect the immobility time in mice. The results indicate that the selective agonist (CP 94253) and antagonists (SB 216641 and GR 127935) of 5-HT1B receptors produce effects that are characteristic of anxiolytics, in the preclinical models used; however, CP 94253 also behaves like an antidepressant drug.
本研究的目的是在常用于预测抗焦虑和抗抑郁样活性的行为测试中，研究选择性5 - HT1B受体激动剂CP 94253、选择性5 - HT1B受体拮抗剂SB 216641以及5 - HT1B/1D受体拮抗剂GR 127935的作用。地西泮和丙咪嗪用作参考药物。在Vogel冲突饮水试验中，CP 94253（1.25 - 5mg/kg）、SB 216641（2.5 - 5mg/kg）和GR 127935（5 - 10mg/kg）显示出与地西泮（2.5 - 5mg/kg）相当的抗焦虑样作用。在高架十字迷宫试验中，也观察到了所有受试化合物的抗焦虑样活性：CP 94253（2.5mg/kg）和SB 216641（5mg/kg）的作用与地西泮（5mg/kg）相似，而GR 127935（高达40mg/kg）的活性较低。在四板试验中，受试化合物（5 - 10mg/kg）产生的抗焦虑样作用比地西泮（2.5 - 5mg/kg）弱。在强迫游泳试验中，CP 94253（5 - 10mg/kg）与丙咪嗪（30mg/kg）一样，表现出抗不动作用，而SB 216641（2.5 - 10mg/kg）和GR 127935（20 - 40mg/kg）对小鼠的不动时间没有影响。结果表明，在所用的临床前模型中，5 - HT1B受体的选择性激动剂（CP 94253）和拮抗剂（SB 216641和GR 127935）产生了抗焦虑药物的特征性作用；然而，CP 94253也表现出抗抑郁药物的特性。
