# Endogenous cannabinoid control of reward substrates

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $53,211

## Abstract

One of the primary functions of the brain is to calculate the most adaptive action for the organism to make under
a given set of environmental conditions. This process requires learning which features in the environment predict
ethological relevance and subsequently deciding which actions to take, given the probable outcome of those
actions. Hence, neural substrates for reward prediction must interact with those controlling behavioral output.
The neuromodulator dopamine is a critical component of this interaction. Dopaminergic neurons in the midbrain
are excited by rewards not predicted by the current environment. However, when stimuli reliably predict reward,
they decrease activity time locked to the reward and shift to the environmental predictors themselves. Therefore,
dopamine is thought of as a teaching signal that broadcasts stimuli-related reward predictions. Data from the
previous funding cycles showed that endocannabinoids in the ventral tegmentum sculpt cue-induced surges in
dopamine release in the nucleus accumbens during reward seeking. We hypothesized, but never unambiguously
demonstrated, that this arises from release of the endocannabinoid 2AG from dopamine neurons themselves,
which lessens their level of inhibition. This disinhibition mechanism is highly conserved as we found that it occurs
during the pursuit of appetitive rewards but also during the avoidance of punishment. However, the precise
excitatory input to the ventral tegmentum responsible for the on-demand release of 2AG from dopamine neurons
is not known. Here, we propose experiments to further elucidate the role of endocannabinoid signaling in
encoding of reward-related cues and its role in motivation.
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## Key facts

- **NIH application ID:** 10487736
- **Project number:** 3R01DA022340-12S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joseph F Cheer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $53,211
- **Award type:** 3
- **Project period:** 2008-03-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10487736

## Citation

> US National Institutes of Health, RePORTER application 10487736, Endogenous cannabinoid control of reward substrates (3R01DA022340-12S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10487736. Licensed CC0.

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