Effects of a selective 5-HT1B receptor agonist and antagonists in animal models of anxiety and depression.

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.