Anxiolytic-like effects of the selective 5-HT 1A receptor antagonist WAY 100635 in non-human primates

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.