# Norepinephrine and dopamine dynamics during conditioned place preference and aversion in dorsal hippocampus

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $48,974

## Abstract

SUMMARY: In 2017, 19.7 million American adults struggled with substance use disorders, and in 2020, nearly
70,000 people died from opioid-involved overdoses. In opioid dependent individuals, environmental stress
perpetuates cravings, and relapse is associated with strong stress responses and reactivity to drug cues.
Unexpected reward and aversive stimuli affect ventral tegmental area (VTA) dopamine (DA) neuron activity, and
studies neuropharmacological studies have revealed DA released from VTA in dorsal hippocampus (CA1)
regulating contextual learning. Locus coeruleus noradrenergic (LC-NE) neurons may also release DA, which has
the potential to affect contextual memory and plasticity in CA1. To address how aversive and rewarding contexts
affect the opioid seeking, we must understand the neuropharmacological properties of norepinephrine (NE) and
DA in opioid-associated contextual memory. The initial process of forming memories is acquisition, while after
memories are reactivated, they are considered versatile before being reconsolidated for long term memory.
While we know noradrenergic and dopaminergic receptors have been implicated in opioid contextual processing,
yet there have not yet been clear pharmacological approaches examining endogenous monoamine release
during contextual behavior. The central hypothesis of this proposal is that DA in CA1 is primarily released from
the VTA, and only VTA-DA is necessary for, and LC-NE only enhances, memory acquisition and reconsolidation.
Aim 1A uses two-photon ex vivo imaging and optogenetics with monoamine sensors to determine
spatiotemporal properties of DA release from VTA terminals in dCA1, while Aim 1B will determine spatiotemporal
properties of NE and DA release from LC in CA1. Using ex vivo pharmacology, we will elucidate which
dopaminergic and noradrenergic mechanisms in CA1 influence the release of DA and NE from their source
regions. Aim 2 will tests the necessity of NE and DA sources for morphine or naloxone place preference
reconsolidation and the necessity of NE and DA for preference acquisition. In Aim 2A, we will simultaneously
measure NE and DA dynamics as we pharmacologically inhibit their soma using chemogenetics to determine
the necessity of VTA and LC in memory reconsolidation of a conditioned place preference or aversion. In Aim
2B, we will test the necessity of NE and DA for memory acquisition of conditioned preference or aversion by
using CRISPR gene-editing to knockdown Dbh (NE-producing enzyme) in LC and Th (DA-producing enzyme)
in VTA. This series of in vitro and in vivo neuropharmacology experiments will elucidate monoamine sufficiency
and necessity in contextual processing to further our understanding of the influence of context in opioid seeking.
This proposal will serve as training in neuropharmacology, two-photon optical imaging, optogenetics,
chemogenetics, gene-editing, and behavioral pharmacology approaches. Ultimately, the training outlined in this
proposal will enhance...

## Key facts

- **NIH application ID:** 10839461
- **Project number:** 5F31DA056148-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Avi Kefir Matarasso
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839461

## Citation

> US National Institutes of Health, RePORTER application 10839461, Norepinephrine and dopamine dynamics during conditioned place preference and aversion in dorsal hippocampus (5F31DA056148-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10839461. Licensed CC0.

---

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