Anxiolytic-like effects of the selective 5-HT1A receptor antagonist WAY 100635 in non-human primates.
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.
Barros
Marilia
M
Department of Physiological Sciences, Institute of Biology, University of Brasilia, CEP 70910-900 Brasilia, DF, Brazil.
Mello
Eldon L
EL
Maior
Rafael S
RS
Müller
Christian P
CP
de Souza Silva
Maria A
MA
Carey
Robert J
RJ
Huston
Joseph P
JP
Tomaz
Carlos
C
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D002144:Callithrix; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide