Notice of Special Interest on Neurobehavioral Mechanisms of Social Isolation and Alcohol Use Disorder (AUD)
Notice Number:

Key Dates

Release Date:

November 12, 2019

First Available Due Date:
June 05, 2020
Expiration Date:
February 08, 2022

Related Announcements


PA-19-055 - Research Project Grant (Parent R01 Clinical Trial Required)

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)

Issued by

National Institute on Alcohol Abuse and Alcoholism (NIAAA)


The purpose of this Notice of Special Interest (NOSI) is to support integrative research studies focusing on understanding the behavioral, cognitive, and neurobiological mechanisms underlying the interactions between social isolation and alcohol use disorder.


Social connections strongly influence individual health and well-being including risks for developing alcohol use disorder (AUD) as well as other substance use disorders and negative health outcomes. Social isolation -the objective and perceived quality of social connections, support, and feelings of loneliness- leads to significant behavioral, cognitive, affective, and neurobiological changes. Social isolation, particularly perceived loneliness, during adolescence and old age, is associated with increased alcohol drinking and risk for (AUD). There is evidence showing that social isolation changes neural systems supporting cognitive, affective, and social functioning. Findings from animal and human studies suggest that multiple brain regions responding to social isolation and the experience of a strong sense of loss in social connections overlap with those associated with addiction, pain, and reward (e.g., the extended amygdala, stratum, insula, anterior cingulate cortex and ventral medial cortex). However, the behavioral, cognitive, and neurobiological mechanism(s) underlying the dynamic interactions between social isolation, alcohol use and addiction are not known.

Despite the potential overlap in neural substrates, little attention has been given to the neurobehavioral mechanisms underlying social isolation and its interactions with AUD. Findings of a recent study in animals suggest that social isolation during adolescence enhances long-term potentiation of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA) and, in turn, increases extinction-resistant alcohol cue conditioning. In addition to reward-centered aspects of addiction, social isolation has the potential to intersect with AUD development through stress and pain mechanisms. Perceived loneliness has been shown to influence the programming of the hypothalamic pituitary adrenocortical (HPA) axis and regulation of the serotonergic and dopaminergic systems resulting in significant changes in sociability and impulsive behaviors and has persistent effects on specific brain regions when experienced at different developmental stages. Stress induced by chronic social isolation can also significantly alter activity of the HPA and expression of neuropeptides in multiple brain regions in rats, causing significant changes in neural activity in the bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and dorsomedial hypothalamus (DMH).

In addition, there is strong evidence indicating common neural substrates underlying social-isolation induced pain perception and AUD. Altered pain perception occurs in individuals with AUD. Social isolation (e.g., social rejection and discrimination) has been shown to induce emotional pain or social pain (i.e., the unpleasant experience associated with actual or potential damage to one’s sense of social connection). Recent human and animal studies indicate that pain experiences induced by social-isolation engage brain regions and neural circuitry associated with physical pain and AUD. Hence, the effects of social isolation and their associated brain mechanisms may interact with pain perception and the development and persistence of AUD.

Social connections and social dysfunction strongly influence AUD development and recovery, yet behavioral and neurobiological mechanisms underlying the multi-system, multi-directional interactions between social isolation, alcohol use and AUD are largely unexplored. Sex, racial/ethnic and gender identification, developmental stages, and aging are also known to influence social isolation effects as well as the manifestation of AUD and, hence, need to be considered when studying social isolation-AUD interactions. Understanding mechanisms and causal relationships underlying social brain function and its relation to AUD is likely to provide more evidence-based effective methods for preventing and treating AUD.

Research Objectives:

The objective of this NOSI is to invite applications with research focus on behavioral, cognitive, affective, and neurobiological mechanisms underlying dynamic interactions between social isolation and alcohol addiction.

Appropriate areas of research may include but are not limited to:

  1. Mechanisms underlying the influence of social isolation (e.g., perceived loneliness and social rejection) on affective and behavioral changes that affect neurobiological systems associated with alcohol use and AUD;
  2. The extent to which neural systems responsive to social isolation interact with neural systems critical to pain perception and alcohol addiction, withdrawal, and relapse;
  3. Mechanisms underlying sex, age, racial/ethnic and gender identification, and other individual differences in the impact of social isolation on alcohol use, and relapse;
  4. Identifying mechanisms underlying cognitive impairment(s) (e.g., in learning, memory, and executive control) associated with AUD that can be reversed by improving objective or perceived social connections and support, or that may be exacerbated by social isolation, making it more difficult to stop alcohol drinking behavior; and
  5. Developing mechanism-focused animal models that demonstrate direct translational linkage to the understanding of and/or alleviating the impact of social isolation on human

Application and Submission Information

This notice applies to due dates on or after June 5, 2019 and subsequent receipt dates through September 8, 2022.

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.

  • PA-19-055 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
  • 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)

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-AA-19-031 (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 contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Benjamin Xu, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-6545

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices