# Imaging presynaptic correlates of cocaine locomotor sensitization with near infrared catecholamine nanosensors

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $222,600

## Abstract

PI: Markita Landry (Assistant Professor, UC Berkeley Chemical and Biomolecular Engineering) Project Abstract
Imaging presynaptic correlates of cocaine locomotor sensitization with near infrared catecholamine nanosensors
Cocaine locomotor sensitization is thought to be, in part, driven by changes in dopamine signaling within the
nucleus accumbens (NAc). One potentially early contributing mechanism is internalization and degradation of
D2 autoreceptors within dopamine neurons (Madhavan et al. 2013) and their long range processes. We recently
developed a technique for imaging dopamine neurotransmission in the striatum using synthetic near infrared
catecholamine nanosensors (nIRCats) (Beyene et al. 2019). nIRCats are compatible with a wide variety of
dopamine receptor drugs, and can resolve individual dopamine release “hotspots” ~2 µm in size. We aim to
determine how cocaine locomotor sensitization affects D2 autoreceptor regulation of dopamine release at
individual nIRCat hotspots. Adult male & female C57/Bl6 mice will undergo a five day locomotor sensitization
protocol (control: saline; cocaine: 15 mg/kg). Twenty-four hours after the final locomotor testing session, acute
brain slices will be prepared from saline or cocaine-treated mice, and will be labeled with nIRCat. Dopamine
release will be electrically evoked within the NAc or dorsal striatum to image dopamine release spatiotemporal
kinetics. Via bath application of 1 µM quinpirole and repeating the stimulation protocol, we will assess the change
in evoked nIRCat ∆F/F to assay presynaptic D2 autoreceptor function. By thus probing dopamine autoreceptor
response to quinpirole, we will compare drug effects across treatment conditions and striatal subregions to
answer if and how repeated cocaine administration influences the regulation of presynaptic dopamine release
by D2 autoreceptors. We predict that quinpirole will show a reduced ability to suppress dopamine release in
cocaine-sensitized animals relative to the saline control, and will explore differences in sensitization across
individual dopamine release sites in striatum and NAc of sensitized animals. This work will establish near infrared
imaging, nIRCat nanosensors, and pharmacology as valuable tools to measure dopamine transients at the level
of individual synapses and to analyze the relationship between their modulation by D2 receptor drugs and
locomotor sensitization.
Landry ABSTRACT AB-1

## Key facts

- **NIH application ID:** 10111141
- **Project number:** 1R03DA052810-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Markita Landry
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $222,600
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111141

## Citation

> US National Institutes of Health, RePORTER application 10111141, Imaging presynaptic correlates of cocaine locomotor sensitization with near infrared catecholamine nanosensors (1R03DA052810-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10111141. Licensed CC0.

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