Endocannabinoids are endogenous agonists of CB1 receptors that are also able to activate TRPV1 receptors when administered in high doses. Such profile may explain the biphasic responses observed in animal models, with compounds that act in the endocannabinoid system. In the forced swim test, CB1 agonists show potential antidepressant-like effect when administered in the ventral medial prefrontal cortex (CPFmv). However, the involvement of TRPV1 receptors in behavioral responses related to depression has been little investigated. In addition to CB1 agonists, NMDA receptors antagonists or inhibitors of NO synthesis, also promote antidepressant-like effect when administered in CPFmv. Activation of CB1 receptors decreases glutamatergic neurotransmission in different brain structures related to emotional control, whereas the activation of TRPV1 receptors increases the levels of glutamate and NO in these structures. In this sense, it is known that the endocannabinoid, glutamatergic and nitrergic systems interact to generate differents behavioral responses. However, little is known about the effects of this interaction on mood disorders such as depression. Therefore, the present study aims to investigate the role of CB1 and TRPV1 in antidepressant-like effect of anandamide, an endocannabinoid, in CPFmv. Moreover, it aims to assess the possible interaction between the endocannabinoid, glutamatergic and nitrergic systems of CPFmv in the modulation of behavioral consequences to stress.
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