title: Stress alters asenapine-induced Fos expression in the Meynert's nucleus: response of adjacent hypocretin and melanin-concentrating hormone neurons in rat.
abstract: OBJECTIVE
  Asenapine (ASE), an atypical antipsychotic drug used in the treatment of schizophrenia, induces Fos expression in forebrain. Effect of ASE on activity of basal nucleus of Meynert (NBM) cells, a part of the striatal-cortical circuits, was studied. We were also interested to reveal whether a chronic unpredictable variable mild stress (CMS) preconditioning might affect the ASE impact.
  
  
  METHODS
  Rats were divided into as follows: controls-vehicle, controls-ASE, stressed-vehicle and stressed-ASE groups. CMS included restrain, social isolation, crowding, swimming and cold applied for 21 days. On the 22nd day, rats were subcutaneously injected with ASE (0.3 mg/kg) or vehicle (saline 300 μl/rat), 90 min prior euthanizing. After transcardial fixation, brains were cut into 30 μm thick coronal sections. Fos protein presence, as indicator of cell activity, was detected by ABC immunohistochemistry. Hypocretin (Hcrt) and melanin-concentrating hormone (MCH) containing cells were visualized with fluorescent dyes.
  
  
  RESULTS
  ASE induced significant increase in Fos expression in NBM in both controls and CMS preconditioned rats in comparison with the related vehicle-treated controls. CMS preconditioning, however, significantly lowered the Fos response to ASE in NBM. From Hrct and MCH cells, only Hcrt ones displayed Fos presence in response to ASE.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that ASE may target a special group of cells occupying NBM, which effect can be modulated by CMS preconditioning. This finding extends a view that ASE impact may extend beyond the classical forebrain target areas common for the action of all antipsychotics and might be helpful in the identification of sites and side effects of its therapeutic actions.
authors.affiliation: a Laboratory of Functional Neuromorphology , Institute of Experimental Endocrinology Slovak Academy of Sciences , Bratislava , Slovakia.
authors.forename: Z
authors.initials: Z
authors.lastname: Majercikova
authors.affiliation: a Laboratory of Functional Neuromorphology , Institute of Experimental Endocrinology Slovak Academy of Sciences , Bratislava , Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Kiss
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D020532:Basal Nucleus of Meynert / Q000166:cytology* / Q000378:metabolism; D003986:Dibenzocycloheptenes; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D007028:Hypothalamic Hormones / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000009:adverse effects; D012934:Social Isolation / Q000523:psychology; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology / Q000473:pathology
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D007028:Hypothalamic Hormones; D008543:Melanins; D016761:Oncogene Proteins v-fos; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; C522667:asenapine
keywords: Asenapine; Chronic unpredictable variable mild stress; Fos expression; Nucleus basalis Meynert; Rat