Sustained corticosterone secretion on postnatal day 11: behavioral and neurochemical effects in adult female and male rats

• Grant number: 14/22395-0
• Support type: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2015
• Effective date (End): February 28, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Deborah Suchecki
• Grantee: Rafael Cabbia
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Evidence indicates that the neonatal period is important for development, due, mainly, to the great plasticity of the central nervous system which is under a maturational process, making the newborn highly vulnerable to intrinsic and extrinsic events. Lack of parental care produces permanent changes in the organism, directing the phenotypic plasticity towards resilience or vulnerability to mental disorders. Among the various paradigms of early life stress, maternal deprivation has been widely used to understand how early stressors maybe affect development. In rats, maternal deprivation for 24 hours leads to adrenal desensitization in the newborn, allowing these glands to respond to different stressors, culminating with exacerbated and prolonged corticosterone secretion, which can interfere with central nervous system maturation. Therefore, the purpose of this study is to examine whether prolonged elevation of corticosterone concentrations, resulting from application of one punctual stressor (saline injection), in animals subjected to maternal deprivation on postnatal day (PND) 11 can generate anxiety and/or depressive like-phenotypes in adulthood, and the underlying changes in the neurochemical profile in brain structures related to these behaviors. Two main groups will be used in these experiments: no maternal deprivation (NPRIV) and maternal deprivation on postnatal day 11 (PRIV). All pups in half of the litters will receive one saline injection (0.9% in volume of 0.1 ml/10 g) two hours before the end of maternal deprivation, whereas the other half of the litters in each group will not receive this stimulus. Thus, four groups will be formed: no maternal deprivation (NPRIV+NSAL), no maternal deprivation + saline injection (NPRIV+SAL), maternal deprivation (PRIV+NSAL) and maternal deprivation + saline injection (PRIV+SAL). Litters will be culled to 4 males and 4 females on postnatal day 1. In adulthood, 1 male and 1 female of each litter will be decapitated without previous being tested (Basal), whereas the remainder of animals in each litter will be evaluated in a behavioral tests battery, applied weekly: Novelty Suppressed Feeding (NSF), Sucrose Positive Contrast Test (SPCT), Social Investigation Test (SI) and Elevated Plus-maze (EPM). After the EPM, one pair of rats (1 male and 1 female) will be decapitated at 15 min, 45 min or 75 min to assess the hormone reactivity to the EPM. The brains will be dissected in frontal cortex, dorsal and ventral hippocampus, amygdala and hypothalamus for determination of monoamine and metabolites concentrations. The data will be analyzed two-way ANOVA, whith Group (NPRIV, PRIV), Punctual Stress (NSAL, SAL) and Time (for hormonal concentrations: Basal, 15, 45, 75 min) as main factors. In case of interaction, Newman-Keuls test will be applied. The level for statistical difference will be set at p<0.05. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CABBIA, RAFAEL; CONSOLI, AMANDA; SUCHECKI, DEBORAH. Association of 24h maternal deprivation with a saline injection in the neonatal period alters adult stress response and brain monoamines in a sex-dependent fashion. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 21, n. 4, p. 333-346, 2018. Web of Science Citations: 4.