Anxiolytic-like effects of the selective 5-HT1A receptor antagonist WAY 100635 in non-human primates

Eur J Pharmacol. 2003 Dec 15;482(1-3):197-203. doi: 10.1016/j.ejphar.2003.09.064.

Abstract

Non-human primates provide important insights into the potential use of 5-HT(1A) receptor antagonists in treating human anxiety disorders and as research tools, given the existent inconsistencies in rodent tests. This study investigated the effects of the selective silent 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide trihydrochloride (WAY 100635), administered systemically, in an ethologically based fear/anxiety test in marmoset monkeys (Callithrix penicillata). Subjects were tested using a figure-eight maze and a taxidermized wild cat as 'predator' stimulus. After seven 30-min maze habituations in the absence of the 'predator', each animal was submitted to four pseudo-randomly assigned 30-min treatment trials in the presence of the 'predator': three WAY 100635 (0.2, 0.4 and 0.8 mg/kg, i.p.) sessions and a saline control trial. The 'predator' stimulus caused a significant fear-induced avoidance of the maze sections closest to where it was presented, indicating an anxiogenic effect. However, WAY 100635 treatment reversed, significantly and dose-dependently, this fear-induced avoidance behavior, while increasing maze exploration. Sedation was not observed. This is the first study to suggest an anxiolytic-like effect of the selective silent 5-HT(1A) receptor antagonist WAY 100635 in non-human primates, indicating its potential use as a therapeutic agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use*
  • Anxiety / drug therapy*
  • Anxiety / psychology
  • Callithrix
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Receptor, Serotonin, 5-HT1A / physiology
  • Serotonin 5-HT1 Receptor Antagonists*
  • Serotonin Antagonists / pharmacology
  • Serotonin Antagonists / therapeutic use*

Substances

  • Anti-Anxiety Agents
  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide