Nucleus Millenium in Stress and Addiction: from molecules to behavior

Gysling, Katia; Andrés, Maria Estela

Abstract

The main goal of the present research proposal is to advance the knowledge of the mechanisms underlying stress-induced relapse to drug seeking contributing to the development of new pharmacological and behavioral strategies to treat substance abuse and addiction. This Núcleo is constituted by a group of researchers organized in the Program in Neurobiology of Drug Addiction (NEDA). Our complementary expertise’s and multidisciplinary approach focus in a common research project will allow us advancing the knowledge of the molecular and neuronal plastic changes underlying the vulnerability to drug abuse observed in individuals exposed to high levels of stress, and stress-induced drug seeking in addicts. This effort will also allow us to improve the impact of our research and the training of young scientists interested in the field at the doctoral and postdoctoral level. Our hypothesis sustains that both chronic stress and withdrawal from chronic cocaine self-administration induce a corticotropin releasing hormone (CRH) receptor-mediated sensitization of medial prefrontal cortex (mPFC) glutamate activity to the ventral tegmental area (VTA) and bed nucleus of stria terminalis (BNST), key brain nuclei in stress and drug addiction. This persistent increase in glutamate release induced by the CRH system could underlie the persistent changes associated to stress and drug addiction. Specific aims of the research proposal are to study: 1) Whether both chronic stress and cocaine experience induce a CRH-dependent sensitization in the VTA and BNST. 2) The mechanisms underlying the CRH-dependent sensitization of VTA glutamate release. 3) The expression of transcription factors Nurr1 and Nur77 in the addictive process, and their role regulating the expression of CRH and urocortin1. 4) The role of insular cortex on craving elicited by stress and on relapse to drug seeking. The Added value of this Núcleo is the development of a multidisciplinary research project using self-administration, the most validated model of drug seeking behavior in drug-experienced animals to study stress-induce relapse to drug seeking at the molecular, neurochemical and anatomical levels. We expect to increase the impact of our research and training of doctoral and postdoctoral fellows from Chile and abroad. As a long-term goal, we expect to contribute to the therapy of drug abuse and to the discussion of public policies regarding drug abuse and addiction. Outreach: 1) Consolidation of a “Center for research, prevention and treatment of drug addiction” at Catholic University working together with the Student Health Service and the Psychiatry Department to increase the awareness of the society regarding the biological basis, consequences and treatment of drug addiction. 2) Diffusion of the scientific advance in drug addiction to the general public and to high school students. Training and networking: 1) To offer a course on the neurobiology of drug addiction for our Ph.D. program. 2) Training of doctoral and postdoctoral fellows in molecular, neurochemical and behavioral aspects of drug addiction. 3) To maintain the Continuing Education Certificate “Neurobiology of drug addiction” directed to professionals working with addicts and biology high school teachers. 4) To consolidate and extend our current collaborations with prestigious foreign scientists and their Institutions.

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Fecha de publicación: 0
Año de Inicio/Término: 26/11/2007 - 22/09/2014
Financiamiento/Sponsor: Millennium Science Initiative ‐ Ministry for Economy, Development, and Tourism