April 3, 2023
PA-20-200 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)
PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
PA-20-190 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)
PA-20-208 - Substance Use/Substance Use Disorder Dissertation Research Award (R36 - Clinical Trials Optional)
PAR-21-208 - Cutting-Edge Basic Research Awards (CEBRA) (R21 Clinical Trial Optional)
National Institute on Drug Abuse (NIDA)
This Notice of Special Interest (NOSI) encourages studies to exploit the unique properties and functions of glial cells and develop strategies to mitigate Central Nervous System (CNS) damage due to acute or chronic exposure to addictive substances or therapeutic avenues for addiction treatments.
Glia play important roles in CNS function, maintenance and repair. These include maintaining CNS homeostasis, supporting calcium, neurotransmitter and oxidative stress signaling pathways, and regulating lipid metabolism and energy production. In neuroinflammation, glial cells also take part in the innate and adaptive CNS responses that are involved in the inflammasome and autophagy pathways. Recent technological developments have accelerated the identification of novel glial functions and their prominent roles in shaping addiction, but gaps remain in how glial cell biology can be used to improve treatment options and outcomes for substance use disorders (SUD). Glia exhibit regional differences in their phenotype, morphology and function in the CNS. Studies show that glial cells reserve domain-specific functions for local neuronal circuitry and can act as stable repositories of spatial information essential for local regulation, but the impact of regional glial function heterogeneity on SUD remains unclear. Glia can directly affect neurobiological processes of drug reward-related behaviors. Evidence suggests that addictive substance use and dependence can result in damage to various neuronal cell types. Repair of such neural damage in SUD may require replenishment and regeneration of neuronal structures and neural circuits affected by the process of addiction. Reprogramming glial cells for such repair may present a promising novel approach for treatment of SUD. Hence, glia are poised to be employed as therapeutic targets for several aspects of addiction. This NOSI focuses on glia-centric strategies for reversing or ameliorating the neural processes set in play by addictive drugs.
Examples of research topic to facilitate the use of glia as therapeutic targets are described in the following categories. Areas of interest include, but are not limited to:
Glia-directed pharmacotherapies for addiction treatments. Glia express several sub-types of dopamine receptors, multiple members of the G protein-coupled receptor (GPCR) super-family, calcium channels, and voltage-gated ion channels that are critical regulators of dopaminergic signaling in the brain reward system. Generating viable SUD treatments that leverage glial cells requires identifying the molecular targets of specific populations of glial cells.
Conversion of glia to neurons for SUD therapy. Emerging studies have demonstrated glia can be reprogrammed into functional neurons in defined brain regions. These approaches are promising for treating various aspects of neurological disorders including SUD, although more work is needed to describe discrete cellular identities and functional features of the glial-derived neurons in their respective circuits.
Cell-cell interaction approach. Acting as architects of the CNS, astrocytes and microglia are involved in synapse formation and clearance, both during and post-development. Oligodendrocytes have major roles in shaping synapse formation, neuronal circuit development, and myelination. Therapeutic applications in SUD that modify interactions between neurons and glia to regulate different synaptic classes in different brain regions in vivo will be a key area of exploration. Approaches such as engineering the cell surface to display functional modules, tools that can fabricate and manipulate cell assemblies and control cell-cell interactions may be explored to advance this area.
Application and Submission Information
This notice applies to due dates on or after June 5, 2023 and subsequent receipt dates through September 8, 2026.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Shang-Yi Anne Tsai, Ph.D.
National Institute on Drug Abuse/Division of Neuroscience and Behavior