R01DA054584

Single-Cell Dissection of Ensembles and Cell Types Mediating Opioid Action in the Rodent Brain - Substance Use Disorder (SUD) is a debilitating condition characterized by compulsive use of a substance, in spite of the subjective recognition of the drawbacks associated with its use.

Chronic use of the substance leads to the development of withdrawal and dependence, hindering intentional controls over its use. Among all substances, opioids are among the ones that pose the greatest negative impact on our society.

Animal and human studies have implicated several brain regions involved in Opioid Use Disorder (OUD), in particular various components of the dopamine system. Major dopamine-containing neurons are clustered in regions of the midbrain called the Substantia Nigra Pars Compacta (SNC) and Ventral Tegmental Area (VTA). Classically, their activities correlate with valence, e.g., promoting approach behavior to rewarding stimuli.

Upstream of them, two major circuits are involved: one including the nucleus accumbens projecting onto the VTA, and the other including the dorsal striatum projecting onto the SNC. The scope of this study is thus to conduct in-depth transcriptomics across the cells of these two circuits to dissect genes, pathways, and cell types mediating opioid action in the mouse brain.

We will use these data to predict driver genes, regulatory regions, pathways, and cell types involved in the emergence of opioid addiction behaviors. Finally, to test the causal role of these predicted drivers, we will use opioid self-administration, a classical paradigm used in the field of addiction.

By combining a rich set of behavioral protocols with state-of-the-art transcriptomics, epigenomics, and computational data analysis, we aim to obtain multi-modal data with an unprecedented level of single-cell resolution for identifying genes, pathways, and cell types affected in mouse models of OUD.

Massachusetts Institute Of Technology

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

Cambridge, Massachusetts 021394301 United States

Single Zip Code

Large scale mapping and/or molecular profiling of ensembles and/or cell-types mediating opioid action in the rodent brain (R01 - Clinical Trial Not Allowed) (PAR-20-241)

Amendment Since initial award the total obligations have increased 400% from $616,630 to $3,083,150.