Reduced hypothalamic NOS activity and CB1 mRNA cannabinoid receptors are related to behavioral impairments in stressed rats.

BURDET B; MAUR, D.G.; DE LAURENTIIS A.; RETTORI V.; ZORRILLA ZUBILETE M.A.

San Diego

Congreso; Neuroscience 2013; 2013

Society for Neuroscience

Chronic stress leads to activation of the hypothalamo-pituitary-adrenal axis (HPA) andchanges in different parameters in limbic areas associated with stress. Thehypothalamus is the main brain structure involved in the neuroendocrine controlof stress and anxiety and it has been demonstrated that nitric oxide (NO), a free radicalproduced by nitric oxide syntase (NOS), participates in these processes. On the otherhand, there is evidence that endocannabinoid system can modulate stress responses.The aim of the present work was to study the effect of chronic restraint stress onbehavioral impairments and the participation of the endocannabinoid system and NO inthese effects (using a NOS inhibitor, L-NAME and a NO donor, Molsidomine).Restraint stress was applied to adult Sprague-Dawley male rats for two hours dailyduring 7 consecutive days (7d). Inhibitory avoidance and elevated plus maze tests, NOSactivity, oxytocin and corticosterone plasma levels and cannabinoid receptor type 1(CB1) levels in hypothalamus were evaluated.A significant decrease (p<0.001) in the activity of hypothalamic total NOS was found instressed animals respect to control (C) animals. The expression of hypothalamic CB1mRNA was significantly reduced (p<0.05) after restraint stress. Oxytocin andcorticosterone plasma levels were significantly increased in stressed rats (p<0.01 andp<0.05 respectively). Moreover, we found a significant decrease in the latency to enterinto the dark compartment in the 7d respect to C (p<0.05) as well as in 7d+Veh andC+L-NAME groups respect to C+Veh (p<0.01 and p<0.05 respectively) in theinhibitory avoidance test. Also, a significant increase in the percentage of entries andtime spent in the open arms in the 7d respect to C (p<0.05) as well as in 7d+Veh andC+L-NAME groups respect to C+Veh (p<0.05) was found in the elevated plus mazetest.In conclusion, our model of stress elicited anxiolytic-like behavior and a deficit inassociative memory that could be related to the decrease in NO production and CB1receptors levels in the hypothalamus. Also the increase in oxytocin plasma levels couldcontribute to the behavioral changes observed.