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

Behav Pharmacol. 2004 Dec;15(8):523-34. doi: 10.1097/00008877-200412000-00001.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / therapeutic use
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Anxiety / drug therapy*
  • Anxiety / psychology
  • Behavior, Animal / drug effects
  • Benzamides / therapeutic use
  • Conflict, Psychological
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Diazepam / therapeutic use
  • Electroshock
  • Exploratory Behavior / drug effects
  • Imipramine / therapeutic use
  • Male
  • Mice
  • Motor Activity / drug effects
  • Oxadiazoles / therapeutic use
  • Piperazines / therapeutic use
  • Pyridines / therapeutic use
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Receptor, Serotonin, 5-HT1B / drug effects*
  • Serotonin Antagonists / therapeutic use*
  • Serotonin Receptor Agonists / therapeutic use*
  • Swimming / psychology

Substances

  • Anti-Anxiety Agents
  • Antidepressive Agents, Tricyclic
  • Benzamides
  • CP 94253
  • N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide
  • Oxadiazoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • GR 127935
  • Imipramine
  • Diazepam