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Participation of the ventral portion of the medial prefrontal cortex on the mediation of stress-induced behavioral consequences

Abstract

In the central nervous system (CNS), the activation of NMDA receptors by glutamate leads to a cascade of events that promote the activation of the enzyme neuronal nitric oxide synthase (nNOS) and subsequent nitric oxide (NO) synthesis. It has been shown that both neurotransmitter systems can be down-regulated by repeated antidepressant treatment. Moreover, the administration of NMDA antagonists or nNOS inhibitors induces antidepressant-like effects in animal models. Therefore, increased levels of such neurotransmitters might mediate the stress-induced behavioral consequences, such as behavioral despair in animals and depression in humans. However, the neurocircuitry involved in such processes remains to be investigated. The involvement of the medial prefrontal cortex (MPFC) in the neurobiology of depression has been controversial since increased as well reduced levels of activity have been described in the brains of depressed individuals. Moreover, studies with lesions of the MPFC in rats submitted to animal models of depression have also produced contradictory results. This could be, at least in part, due to the fact that the MPFC comprises dorsal and ventral portions which may play different roles in regulating emotional responses to stress. However, this hypothesis has not been investigated so far. Therefore, we are aimed at investigating the involvement of the ventral portion of the MPFC (vMPFC) in mediating the behavioral consequences induced by the exposure an animal model of depression. For this purpose, we will perform studies with transient and reversible inactivation of the vMPFC, separately in its prelimbic and infralimbic regions, in order to assess possible functional differences among these to subnuclei. In addition, we will evaluate the involvement of glutamate and NO in infralimbic and prelimbic cortices in the mediation of stress-induced behavioral consequences. (AU)