Differential modulation of the contextual conditioned emotional response by CB1 and TRPV1 receptors in the ventromedial prefrontal cortex: Possible involvement of NMDA/nitric oxide-related mechanisms

Background: Blockade of cannabinoid CB1 or vanilloid TRPV1 receptors in the ventromedial prefrontal cortex of rats respectively increases or decreases the conditioned emotional response during re-exposure to a context previously paired with footshocks. Although these mechanisms are unknown, they may involve local modulation of glutamatergic and nitrergic signaling. Aim: We investigated whether these mechanisms are involved in the reported effects of CB1 and TRPV1 modulation in the ventromedial prefrontal cortex. Methods: Freezing behavior and autonomic parameters were recorded during the conditioned response expression. Results: The CB1 receptors antagonist NIDA, or the TRPV1 agonist capsaicin (CPS) in the ventromedial prefrontal cortex increased the conditioned emotional response expression, and these effects were prevented by TRPV1 and CB1 antagonism, respectively. The increased conditioned emotional response evoked by NIDA and CPS were prevented by an NMDA antagonist or a neuronal nitric oxide synthase inhibitor. A nitric oxide scavenger or a soluble guanylate cyclase inhibitor prevented only the NIDA effects and the CPS effect was prevented by a non-selective antioxidant drug, as nitric oxide can also induce reactive oxygen species production. Conclusion: Our results suggest that CB1 and TRPV1 receptors in the ventromedial prefrontal cortex differently modulate the expression of conditioned emotional response through glutamatergic and nitrergic mechanisms, although different pathways may be involved. (AU)