# Targeting Dopamine-Mediated Social Reward Sensitivity to Remediate Social Disconnection

> **NIH NIH R61** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $1,423,718

## Abstract

Social relationships contribute enormously to our health and well-being. Social disconnection is a common and
disabling feature of anxiety and depressive disorders that does not respond sufficiently to our best available
treatments. These outcomes suggest first-line treatments do not adequately engage the mechanisms that
support positive connections with others. Animal and human research suggests the dopamine system plays an
important role in responding to social reward cues and opportunities that drive our motivation and behavior
toward connecting with others. Diminished social reward anticipation is observed across anxiety and
depressive disorders – pointing to a trans-diagnostic mechanism that may underpin social disconnection.
Directly modulating dopaminergic functioning in a dose-dependent manner would provide a strong causal test
of social reward-mediated disconnection pathways. This is important because first-line pharmacotherapies for
anxiety and depression do not directly target this system, which may explain in part why social disconnection
persists for many patients following treatment. The proposed two-phase, milestone-driven project will address
this gap by testing the hypothesis that modulating the dopamine system pharmacologically will enhance social
reward anticipation (the treatment target) and therefore improve social connectedness (primary outcome) in
individuals with clinical levels of anxiety or depression. We will selectively engage this system using
pramipexole – a D2/D3 dopamine receptor agonist shown to enhance dopamine signaling in the striatum –
thereby providing a strong proof of mechanism test. The R61 project will evaluate dose-dependent effects of
pramipexole on striatal activation during social reward anticipation (primary outcome) and opportunities to
disclose to others. Secondary outcomes will be measured during dyadic affiliation and shared experiences
tasks. Aim 1 will test the hypothesis that pramipexole increases social reward anticipation compared to placebo
following 6 weeks of treatment. Aim 2 will determine which dose of pramipexole produces a greater effect on
social reward anticipation. Pramipexole blood concentrations will be used to confirm dose-dependent target
engagement. If pramipexole is superior to placebo in increasing striatal activation to social reward anticipation,
the R33 project will attempt to replicate the R61 findings (Aim 1) and examine whether increases in social
reward anticipation are associated with improvements in social connectedness (Aim 2) following a 6-week
double-blind, randomized, placebo-controlled trial (dose informed by the R61). Secondary outcomes will be
change in positive and negative valence symptoms (e.g., social anhedonia, anxiety, depression). An
exploratory aim will examine treatment effects on negative valence processes (e.g., threat sensitivity). Positive
findings would validate a new CNS target for remediating social disconnection that could be studied in large...

## Key facts

- **NIH application ID:** 10572245
- **Project number:** 1R61MH129380-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Franklin R. Schneier
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,423,718
- **Award type:** 1
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10572245

## Citation

> US National Institutes of Health, RePORTER application 10572245, Targeting Dopamine-Mediated Social Reward Sensitivity to Remediate Social Disconnection (1R61MH129380-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10572245. Licensed CC0.

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