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.