The discovery of the anxiolytic properties of antidepressants (ADs) represented a great advance in the treatment of anxiety disorders. Clinical observations that selective serotonin re-uptake inhibitors are the first choice treatment for these pathologies highlighted the importance of serotonin in this process. Other evidence shows that the therapeutic effects of ADs develop only after chronic administration, suggesting that long-term neural adaptations are involved in the model of action of these drugs. It has been hypothesized that a progressive desensitization of 5-HT1A inhibitory autosomic receptors and/or alterations in postsynaptic 5-HT1A and 5-HT2 receptors sensitivity in forebrain structures, such as the hippocampus and amygdala, are involved in the delayed onset of ADs benefic effects. Studies using the elevated T-maze (ETM) revealed the involvement of 5-HT1A receptors on the basolateral nucleus of the amygdala (BLA) in the anxiolytic effect observed after chronic treatment with AD. They also evidenced the recruitment of 5-HT2C receptors of this same structure, in the anxiogenic effect observed after acute treatment with the same drugs. Compelling evidence shows the involvement of the dorsal hippocampus (DH) in the regulation anxiety-related defensive responses. It has been reported that in this brain area whereas stimulation of 5-HT1A receptors causes anxiogenic-like effect in the ETM, activation of 5-HT2C receptors causes the opposite effect. The aim of this study is to investigate the role of 5-HT1A and 5-HT2C of the DH on the anxiolytic and anxiogenic effects caused by ADs, as measured by different animal models of anxiety. To this end, both pharmacological (studies with antagonists) and genetic approaches (RNA interference) will be used.
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