Depression is a substantial public health problem; it is the second cause of disability worldwide. Our group report on a new treatment strategy based on the administration of small interference RNA (siRNA) to suppress 5-HT1A-autoreceptor-mediated negative feedback mechanisms. We developed a conjugated siRNA (C-1A-siRNA) by covalently binding siRNA targeting 5-HT1AR mRNA with the SSRI sertraline in order to concentrate it in serotonin axons. The image shows merge of TPH-ir serotonin neurons (in blue) and Cy3-labeled C-oligonucleotide (in red-pink). In parallel, intracerebroventricular C-1A-siRNA infusion markedly decreased presynaptic 5 HT1A-autoreceptor expression in the midbrain dorsal raphe (DR) without affecting postsynaptic 5-HT1AR expression in hippocampus (HPC), eliciting robust antidepressant effects. For more info on this topic, please refer to the article by Bortolozzi et al., Mol Psychiatry advance online publication, August 2, 2011; doi:10.1038/mp.2011.92.