The purpose of this notice is to encourage research project submissions examining the role of neuroimmune signaling in the CNS in relation to: the trajectory (i.e. initiation, escalation, and maintenance) of drug misuse; consequences of chronic exposure to misused drugs; abstinence and withdrawal from prolonged use; and relapse or reinstatement of drug taking at molecular, cellular, circuit, or behavioral levels.

Background

Repeated exposure to drugs of abuse can cause changes in neuronal structure and function that contribute to and sustain drug use. Research has largely focused on the interactions of drugs with specific neuronal targets, and on the consequences of drug exposure on neuronal function, excitability, neuroplasticity, and neurochemistry. However, emerging evidence shows that neuroimmune factors, released from both glia or neurons, can modulate neuronal structure and function, either by affecting neuron-glia interactions or through direct effects on neurons. Yet the role of neuroimmune signaling in the modulation of neuronal function as it affects the expression of substance use behaviors is poorly understood. Research has shown that drugs of abuse, including methamphetamine, morphine, cocaine and nicotine, can elicit neuroinflammatory responses. Stress, an important contributor to relapse, can also elicit neuroimmune responses. Consequently, neuroimmune signaling may be integral to mechanisms underlying drug misuse, addiction, and other consequences of repeated drug use. Further, because the molecular targets and receptors for abused substances differ, the complement of neuroimmune factors affected by exposure to a particular drug may be drug-specific. Research to identify the commonalities between specific drugs of abuse, the neuroimmune factors released by drug use, and the neuroanatomical specificity of the responses is needed. It is expected that the contributing actions of neuroimmune signaling to addictive behaviors are most likely due not to obvious brain damage and overt pathology, but to the consequences of such signaling in altering specific molecular and cellular processes within glia, neurons, and neural circuits.

Research Objectives

NIDA seeks to stimulate research on the identification and characterization of neuroimmune factors and the mechanism(s) by which these factors may mediate substance use, misuse, and addictive behaviors. NIDA is particularly interested in the identity, diversity, chronicity, and functional consequences of the neuroimmune factors released in response to intermittent or chronic drug exposure or withdrawal, their effects on neuron-glia signaling, and how these factors may facilitate or protect against developing substance use disorders. Applications may focus on all areas of research relevant to understanding neuroimmune signaling in substance misuse, such as genetic and epigenetic components; molecular, cellular, and physiological responses; neural circuitry; and behavior. Applications may propose to study lifespan and vulnerable periods, comorbidity, and sex differences. Applications that incorporate clear behavioral measures are especially encouraged.

Application and Submission Information

This notice applies to due dates on or after June 5, 2020 and subsequent receipt dates through September 8, 2023.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice.

• PA-19-056: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

• PA-19-091: NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

• PA-19-053: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

• PA-19-092: NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

• PAR-19-134: Research Enhancement Award Program (REAP) for Health Professional Schools and Graduate Schools (R15 Clinical Trial Not Allowed)

• PA-18-591: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DA-20-046” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Scientific/Research Contact(s)

Roger G Sorensen, Ph.D., MPA
National Institute on Drug Abuse (NIDA)
Telephone: (301) 443-3205
Email: rsorense@nida.nih.gov