The medial prefrontal cortex modulates the baroreflex activity through the CB1 receptor/NMDA receptor/Nitric Oxide pathway

Medial prefrontal cortex (MPFC) NMDA receptor/Nitric Oxide (NO) pathway enhances the baroreflex activity. CB1 receptors decrease glutamate release and negatively modulate the baroreflex response in the MPFC. Therefore the aim of this study is to investigate if the MPFC CB1 receptors modulate the baroreflex by influencing the NMDA receptor/NO pathway. Male Wistar rats had stainless steel guide cannulae implanted into the MPFC and baroreflex was activated by intravenous infusion of phenylephrine or sodium nitroprusside. A second catheter was implanted into the femoral artery for cardiovascular measurements. The CB1 receptor antagonist, AM251 (100 nmol/200 nL), injected into the MPFC increased both bradycardic (F_(2,14) = 9.52; p < 0.05, n = 5) and tachycardic (F_(2,14) = 4.15; p < 0.05, n = 5) reflex responses. This effect was prevented by MPFC treatment with ineffective doses of the NMDA receptor antagonist, AP7 (0.4 nmol/200 nL; bradycardia: F_(2,17) = 0.66; p > 0.05, and tachycardia: F_(2,17) = 0.33; p > 0.05, n = 6), the neuronal NO synthase inhibitor, n-propyl (8 pmol/200 nL; bradycardia: F_(2,17) = 0.34; p > 0.05, and tachycardia: F_(2,17) = 0.26; p > 0.05, n = 6); the extracellular NO scavenger, c-PTIO (0.2 nmol/200 nL; bradycardia: F_(2,17) = 0.40; p > 0.05, and tachycardia: F_(2,17) = 1.44; p > 0.05, n = 6); the guanilate cyclase inhibitor, ODQ (0.2 nmol/200 nL; bradycardia: F_(2,17) = 0.11; p > 0.05, and tachycardia: F_(2,17) = 0.28; p > 0.05, n = 6), previously to the microinjection of AM251 in the same dose. In conclusion, the results show that the MPFC CB1 receptors decrease the baroreflex activity by reducing the glutamate release and the NO production by the NMDA receptors.