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Although the atypical antipsychotics clozapine and olanzapine are effective for depression and anxiety in schizophrenia, as demonstrated by animal model studies, this has not been clarified for asenapine. Therefore, we compared the effects of asenapine in the conditioned fear stress model with those of clozapine and olanzapine.<\/jats:p><\/jats:sec><jats:sec id=\"S092427081600017X_abs2\" sec-type=\"general\"><jats:title>Method<\/jats:title><jats:p>Rats were individually fear conditioned using electrical foot shock in a Skinner box. Approximately 24 h later, individual animals were returned to the same Skinner box (without electrical shock) and their freezing behaviour was observed for 5 min. Animals were treated with asenapine, clozapine, olanzapine, the 5-HT<jats:sub>1A<\/jats:sub>receptor partial agonist buspirone, or the 5-HT<jats:sub>2C<\/jats:sub>receptor antagonist SB242084 at 30 min before freezing behaviour assessment. The 5-HT<jats:sub>1A<\/jats:sub>receptor antagonist WAY100635 or the 5-HT<jats:sub>2C<\/jats:sub>receptor agonist Ro60-0175 was also used concomitantly with asenapine. The effects of asenapine, clozapine, and olanzapine on serotonin release in the rat hippocampus were also measured using<jats:italic>in vivo<\/jats:italic>microdialysis.<\/jats:p><\/jats:sec><jats:sec id=\"S092427081600017X_abs3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Asenapine reduced freezing behaviour, while neither clozapine nor olanzapine reduced freezing behaviour. Buspirone and SB242084 also reduced freezing behaviour. The effect of asenapine in reducing freezing behaviour was not altered by the concomitant administration of WAY100635 or Ro60-0175. Both asenapine and clozapine, but not olanzapine, increased serotonin release in the rat hippocampus.<\/jats:p><\/jats:sec><jats:sec id=\"S092427081600017X_abs4\" sec-type=\"conclusion\"><jats:title>Conclusion<\/jats:title><jats:p>Asenapine may have superior therapeutic effect on anxiety symptoms than other agents, although the underlying mechanism of its anxiolytic activity remains unknown.<\/jats:p><\/jats:sec>","DOI":"10.1017\/neu.2016.17","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T06:52:20Z","timestamp":1461221540000},"page":"327-336","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":14,"title":["Asenapine reduces anxiety-related behaviours in rat conditioned fear stress 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