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

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de Oliveira, Rodolpho Pereira ; de Andrade, Jose Simoes ; Spina, Marianna ; Chamon, Joao Vitor ; Dias Silva, Paulo Henrique ; Werder, Ana Keyla ; Ortolani, Daniela ; Cardoso Thomaz, Lucas de Santana ; Romariz, Simone ; Ribeiro, Daniel Araki ; Longo, Beatriz Monteiro ; Spadari, Regina Celia ; Viana, Milena de Barros ; Melo-Thomas, Liana ; Cespedes, Isabel Cristina ; Barbosa da Silva, Regina Claudia

• Document type: Journal article
• Source: PLoS One; v. 17, n. 3, p. 19-pg., 2022-03-03.

Abstract

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. (AU)

• FAPESP's process: 17/17051-8 - Participation of the GABAergic neurotransmission of the inferior colliculus, via activation of 5-HT2A receptors, and its neuroanatomic correlates in the mediation of pre-pulse inhibition response of the acoustic startle reflex and social interaction in ma
• Grantee: Regina Cláudia Barbosa da Silva
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/16634-1 - Effects of acute restraint stress and clozapine treatment in the modulation of prepulse inhibition of the acoustic startle reflex, novel object recognition, social interaction and their neurophysiological correlations in rats
• Grantee: Regina Cláudia Barbosa da Silva
• Support Opportunities: Regular Research Grants