Role of 2-AG in the proneurogenic and bahavioral effects of escitalopram

• Grant number: 17/04700-8
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2017
• Effective date (End): December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal researcher: Alline Cristina de Campos
• Grantee: Paula Carolina Duarte de Souza
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 15/05551-0 - Investigation of the involvement of endocannabinoid system on behavioral and plastic effects of antidepressant drugs, AP.JP

Abstract

Despite their therapeutic efficacy, antidepressant (AD) treatment is associated with a delayed response of, at least, 4 weeks, considerable side effects and low rates of response due treatment-resistance. Several theories, related or not to the monoamiergic theory of Depression, tried to explain the delayed response of AD, but the common sense is that AD repeated treatment induces long-term plastic changes in the SNC mainly by modulating serotonergic neurotransmission (e.g. desensitization of presynaptic 1A serotonergic receptors, increase in hippocampal proliferative processes, dendritic remodeling etc). Morever, Serotonergic and Cannabinoid neurotransmission may also interacts to promote their behavioral and plastic effects. Chronic treatment with AD modulates the expression of CB1 receptors and increases levels of Endocannabinoids- ECBs (Anandamide-AEA and 2-arachidonoylglycerol 2-AG) in the hippocampus and in medial prefrontal cortex (mPFC), brain areas involved in the control of depressive states and anxiety disorders. Moreover, both serotonergic and ECBs system are involved in plastic processes of SNC such as dendritic remodeling, production of neurotrophins and neurogenesis, processes that are up regulated after chronic AD treatment. In the present work, we aim to test the hypothesis that AD chronic treatment interacts with the endocannabinoid 2-AG to facilitate adult hippocampal neurogenesis and, as consequence, behavioral effects. (AU)