Clozapine prevented social interaction deficits and reduced c-Fos immunoreactivity expression in several brain areas of rats exposed to acute restraint stress.

Autor: de Oliveira RP; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., de Andrade JS; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Spina M; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Chamon JV; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Silva PHD; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Werder AK; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Ortolani D; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Thomaz LSC; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Romariz S; Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP/SP), São Paulo, Brazil., Ribeiro DA; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Longo BM; Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP/SP), São Paulo, Brazil., Spadari RC; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Viana MB; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil., Melo-Thomas L; Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-Universityof Marburg, Marburg, Germany.; Marburg Center for Mind, Brain, and Behavior (MCMBB), Marburg, Marburg, Germany., Céspedes IC; Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil., da Silva RCB; Departamento de Biociências, Universidade Federal de São Paulo (UNIFESP), Santos (SP), Brazil.; Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Mar 03; Vol. 17 (3), pp. e0262728. Date of Electronic Publication: 2022 Mar 03 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0262728
Abstrakt: In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.
Competing Interests: The authors report no conflicts of interest.
Databáze: MEDLINE
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