EPA-1474 – Psychosocial stress and psychiatric phenotypes: endocannabinoids and cannabinoid receptor (CBR) expression in cortico-striatal connectivity

Abstract

to investigate the consequences of chronic psychosocial stress on behavior, endocannabinoids and CBR expression in prefrontal cortex (PFC) and striatum of mice. Psychosocial stress was induced in adult C57Bl/6 mice by resident-intruder paradigm (Brzózka et al. 2011). After 3 weeks daily exposure to psychosocial stress for 1 hour, animals were studied during the rodent active phase (night) by behavioral tests such as Functional Observational Battery (FOB), Rota-Rod (R-R), Open Field (OF), Prepulse Inhibition test (PPI). After behavioral testing, mice were sacrificed. 4 mice brains (prefrontal cortex, dorsal striatum) were studied by LC-MS to estimate the concentration of anandamide (AEA), 2- arachidonoylglycerol (2-AG), N-oleoylethanolamine (OEA), palmitoylethanolamide (PEA) (coll. di Marzo). In Situ Hybridization (ISH)and Immunohistochemistry (IHCH) against CB1 receptor were performed on free floating brain coronal sections fixed by 4% paraformaldehyde (coll del Río). 1. After psychosocial stress, mice displayed lower body weight (p<0.01), higher scratching and miccions activity compared to controls (p<0.05), decreased number of falls (p<0.01) and increased latency (p<0.05) in Rotarod. No effects in PPI were found. 2. In the same mice psychosocial stress reduced AEA levels in dorsal striatum and PFC (p<0.05). Endocannabinoids significantly showed an inverse relationship in PFC compared to striatum in control mice (AEA, p<0.001; 2-AG, p<0.001; OEA, p<0.001) and in psychosocially stressed mice (PEA, p<0.001; OEA, p<0.001). 3. Psychosocial stress increased the protein CBR1 expression in striatum (p<0.05) but not in prefrontal cortex. Chronic psychosocial stress significantly changes behavior, endocannabinoids, CB receptor function and the striatal-cortical connectivity. These changes may contribute to vulnerability for psychosis and addiction.