# Neuropeptides, Social Stress and Drugs of Abuse

> **NIH NIH R01** · TUFTS UNIVERSITY MEDFORD · 2021 · $13,728

## Abstract

Project Summary
 The rationale for the current specific aims builds on the consistent epidemiological finding that social
stress contributes critically to all phases of the addiction cycle, from initiation to escalation to relapse. The
close link between social stress and drug use is based on reports from emergency rooms treating victims of
violence and statistics from the criminal justice system on violent crimes committed by drug users as well as
epidemiological evidence and neurobiological data. The overarching question to be answered by the proposed
research is: what is the mechanistic link between social stress and escalated cocaine self-administration? Our
special emphasis is on how corticotropin releasing factor (CRF, often referred to as CRH) modulates
mesocorticolimbic dopamine (DA) systems. The CRF system is of continued interest, not only because it is
critical to the initiation of the endocrine stress response, but its extra-hypothalamic localization and action are
of significance in stress disorders and represent potential targets for therapeutic intervention.
 Specific Aim One tests the hypothesis that highly aversive social stress amplifies intensely rewarding
cocaine self-administration by action on CRF and dopamine (DA) in microcircuits from the posterior ventral
tegmental area (pVTA) to the dorsal raphe nuclei (DRN). Neuroanatomical tract tracing is employed to identify
the synaptic contacts with DA neurons as a source of CRF input. In vivo microdialysis in the terminals of these
microcircuits are used to characterize the dynamic neuroadaptions that contribute to the stress-induced
escalation of cocaine self-administration (acquisition, maintenance, binge, relapse).
 Specific Aim Two tests the hypothesis that activation and inhibition of specific CRF cell groups in the VTA-
DRN microcircuit modulate cocaine self-administration. In vivo optogenetics and, in parallel, Gq- or Gi-
DREADD in mice expressing Channelrhodopsin specifically in CRF neurons (ChR/Crh mice) will be used to
activate CRF inputs into the VTA or inhibit with archaerhodopsin. Microinjections CRFR1, CRFR2 and binding
protein antagonists and agonists into the VTA-DRN microcircuit will identify targets for preventing and
reversing effects of social defeat stress or optogenetic activation that escalate cocaine self-administration.
 A special feature of the proposed work is the test of the hypothesis that social stress-escalated cocaine
self-administration is buffered in a sex-specific manner.

## Key facts

- **NIH application ID:** 10399771
- **Project number:** 3R01DA031734-10S1
- **Recipient organization:** TUFTS UNIVERSITY MEDFORD
- **Principal Investigator:** KLAUS A MICZEK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $13,728
- **Award type:** 3
- **Project period:** 2011-07-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399771

## Citation

> US National Institutes of Health, RePORTER application 10399771, Neuropeptides, Social Stress and Drugs of Abuse (3R01DA031734-10S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399771. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*