# Monitoring real-time adenosine release in the NAc with fast-scan cyclic voltammetry

> **NIH NIH R21** · UNIVERSITY OF COLORADO · 2020 · $192,500

## Abstract

Project Summary
 Drug addiction is characterized by cycles of compulsive drug use followed by periods of abstinence and
relapse. Cues associated with prior drug use elicits drug craving that is highly associated with drug relapse.
Addicted individuals are also more likely to exhibit changes in behavior in nondrug situations, such as
increased risk taking and impulsiveness, and decreased motivation toward effortful activities. These findings
suggest that chronic drug use induces persistent changes in the neural circuits that normally process
associative learning and motivated behavior more generally. The ability of stimuli to subsequently elicit
approach behavior has largely been attributed to dopamine signaling in the nucleus accumbens. This proposal
will open a new avenue of exploration by providing unprecedented analysis of rapid, transient adenosine
signaling in the nucleus accumbens by studying adenosine release kinetics in cocaine-naïve and cocaine-
experienced animals. Adenosine is known to produce a multitude of functions in the brain that have largely
been attributed to the basal tone of intra- and extracellular adenosine. Our current knowledge of adenosine
signaling in the mesolimbic circuit is derived from studies largely examining adenosine receptor functions using
genetic models and pharmacological agents. Phasic adenosine release, however, is a poorly understood
phenomenon largely due to the challenges associated with measuring adenosine release with sufficient
sensitivity and spatiotemporal resolution. Our preliminary findings demonstrate that fast-scan cyclic
voltammetry can be used successfully in awake, behaving animals to measure phasic adenosine release
under naturalistic learning conditions. The studies in Aim 1 will characterize adenosine signaling kinetics in the
nucleus accumbens in cocaine-naïve and cocaine-experienced rats. These studies are expected to provide
novel data illustrating that prior cocaine experience disrupts phasic adenosine signaling kinetics in the nucleus
accumbens and produces differential sensitivity on adenosine signaling in response to the adenosine
antagonist caffeine. The studies in Aim 2 will evaluate the role of adenosine neurotransmission in the nucleus
accumbens during a Pavlovian discrimination task. These studies are expected to provide novel data
illustrating that 1) adenosine signaling is rapid (sub-second) and tracks behaviorally-relevant events in real
time, 2) adenosine and dopamine co-transmission is temporally coordinated to encode distinct aspects of
Pavlovian associations, and 3) that cocaine experience alters both the phasic release of adenosine and
disrupts the functional balance in adenosine and DA signaling in the nucleus accumbens that is necessary for
learning. Together, the proposed studies will significantly advance our understanding of adenosine signaling in
the nucleus accumbens for both drug addiction and naturalistic learning.

## Key facts

- **NIH application ID:** 9868986
- **Project number:** 5R21DA045952-02
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Ryan K Bachtell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-02-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868986

## Citation

> US National Institutes of Health, RePORTER application 9868986, Monitoring real-time adenosine release in the NAc with fast-scan cyclic voltammetry (5R21DA045952-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9868986. Licensed CC0.

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