Effect of administration of fluoxetine and imipramine on serotonergic neurotransmission in different subregions of the dorsal raphe nucleus and dorsal periaqueductal gray of rats exposed to model elevated T maze

Abstract

The mechanisms of anxiolytic and panicolytic actions of antidepressant drugs (ADs) have been the subject of great interest. Our research group has demonstrated that in animals treated chronically with ADs occurs facilitation of neurotransmission mediated by serotonergic 5-HT1A and 5-HT2A receptors in the periaqueductal gray (PAG). This change is associated with the inhibitory effect of ADs on the expression of escape behavior, considered a panicolytic-like response. However, some aspects of the involvement of 5-HT2A receptors and other subtypes of serotonin receptors present in PAG, such as 5-HT2C, in mediating the effects of ADs in experimental anxiety are still poorly understood. In this study, we will investigate if the anti-scape effect caused by chronic administration of fluoxetine and imipramine in the elevated T-maze (LTE) is blocked by administration of receptor 5-HT2A antagonist in the SCPD, as occur with the microinjection of receptor 5 -HT1A antagonists. We will also verify if the blockade of 5-HT2C receptors in the SCPD interferes with the anxiogenic effect caused by acute administration of ADs and if the reactivity of these receptors is changed after prolonged treatment with the same drugs. In the second stage of the study, we will investigate the profile of neuronal activation of different dorsal raphe nucleus subregions (DRN) (evaluating the expression of Fos protein, with double-labeled for the enzyme tryptophan hydroxylase), after acute and chronic administration of imipramine and fluoxetine. The DRN is the main source of serotonergic innervation to the PAG. Although many studies show the importance of alterations in the functioning of serotonergic neurons of the DRN to the ADs effects, it is still unknown whether these alterations may be heterogeneous between different sub-regions of this nucleus.