title: Effect of acute asenapine treatment on Fos expression in the forebrain structures under normal conditions and mild stress preconditioning in the rat.
abstract: Asenapine (ASE) is a novel atypical antipsychotic drug approved for the treatment of schizophrenia and bipolar disorder. Stress is an inseparable part of the human life, which may interfere with the therapeutic effect of different drugs. The aim of the present study was: (1) to delineate the quantitative and qualitative profiles of the ASE effect on Fos expression in the striatum, septum, nucleus accumbens, and the prefrontal cortex and (2) to find out whether a chronic unpredictable variable mild stress (CMS) preconditioning may modify the effect of acute ASE treatment. Stress paradigms included restrain, social isolation, crowding, swimming, and cold. The animals were exposed to CMS for 21 days and on the 22nd day received an injection of vehicle (saline 300 μl/rat s.c.) or ASE (0.3mg/kg s.c.). They were sacrificed 90 min after the treatments. Fos protein was visualized by avidin biotin peroxidase (ABC). Four groups of animals were investigated: controls+vehicle, controls+ASE, CMS+vehicle, and CMS+ASE. The number of Fos labeled neurons was calculated per total investigated area, which was selective for each structure, and also recalculated per unified sector. ASE treatment induced significant and very similar increase of the Fos expression in both ASE control and ASE CMS animals in comparison with saline control and CMS ones. Moreover, ASE induced regional differences in the number of Fos-positive neurons. In both ASE groups most pronounced response in the number of Fos profiles occurred in the dorsolateral striatum, ventrolateral septum, shell of the nucleus accumbens, and the medial prefrontal cortex. Mild Fos response was seen in the dorsomedial and ventromedial striatum and core of the nucleus accumbens. No response was seen in the dorsolateral septum. The present paper demonstrates for the first time the character of the Fos distribution in the forebrain structures induced by acute ASE treatment as well as ASE response to 21 days CMS preconditioning. The study provides an important comparative background that may help in the further understanding of the effect of ASE on the brain activation as well as its responsiveness to CMS challenges.
authors.affiliation: Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Majercikova
authors.affiliation: Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia.
authors.forename: Alena
authors.initials: A
authors.lastname: Cernackova
authors.affiliation: Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia.
authors.forename: Lubica
authors.initials: L
authors.lastname: Horvathova
authors.affiliation: Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia.
authors.forename: Jana
authors.initials: J
authors.lastname: Osacka
authors.affiliation: Department of Psychiatry, Faculty of Medicine in Bratislava, Comenius University, Mickiewiczova 13, 81369 Bratislava, Slovakia.
authors.forename: Jan
authors.initials: J
authors.lastname: Pecenak
authors.affiliation: Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology Slovak Academy of Sciences, Vlarska 3, 83306 Bratislava, Slovakia. Electronic address: ueenkiss@savba.sk.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiss
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D016760:Proto-Oncogene Proteins c-fos; C522667:asenapine
keywords: Asenapine; Chronic unpredictable variable mild stress (CMS); Fos expression; Rat