Consequences of social isolation stress during adolescence on ethanol-induced locomotor stimulation: role of glucocorticoids and the endocannabinoid system

• Grant number: 22/02387-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2022
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Fabio Cardoso Cruz
• Grantee: Mariana Garcia Barbeiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Chronic exposure to stress is an important risk factor for neuropsychiatric disorders, including ethanol use disorders. Social isolation during adolescence is an animal model that has been used to study the consequences of social stress during this ontogenic phase of intense brain development. The activation of the hypothalamic-pituitary-adrenal (HPA) axis, which culminates in the release of glucocorticoids into the bloodstream, represents one of the main physiological responses to stress. However, chronic exposure to stressors may lead to dysregulation of HPA axis activity, which seems to be associated with increased vulnerability to psychiatric disorders, such as ethanol use disorders. Furthermore, repeated exposure to stress seems to affect the HPA axis negative feedback mechanism, exerted by glucocorticoid (GR), mineralocorticoid (MR), and cannabinoid type 1 (CB1) receptors. Therefore, the present project aims to evaluate the consequences of social isolation stress during adolescence on ethanol-induced locomotor stimulation, plasma corticosterone levels, and GR, MR, and CB1 receptors expression, in the hypothalamus, in males Swiss mice (experiment 1). The study also aims to investigate the consequences of social isolation stress on locomotor activity and hypothalamic neuronal activation in response to acute ethanol treatment, after challenge with a heterotypic stressor (experiment 2).(AU)