# Reward Homeostasis, Accumbens AMPA Receptor Trafficking and Drug Abuse

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $190,688

## Abstract

Project Summary
Loss of natural reward is a recognized risk factor for drug abuse and addiction. In animal models, loss of
social or sexual contact, removal from enriched housing, and decreased access to and consumption of food
have all been shown to increase drug-seeking and self-administration. Past research in our laboratory has
shown that food restriction decreases basal dopamine transmission in nucleus accumbens and induces
synaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs). Behavioral studies, using
multiple protocols, have shown these CP-AMPARs to mediate the enhanced responsiveness of food restricted
rats to drugs of abuse and environmental contexts previously paired with their subjective effects. These results
have been considered in conjunction with those from other laboratories indicating that synaptic insertion of CP-
AMPARs is a homeostatic response to deprivation of input to neurons in culture, and occurs in vivo after
withdrawal from exceptional reward stimulation (e.g. drugs of abuse and “junk food”). This project begins to
test the novel hypothesis that synaptic insertion of CP-AMPARs in NAc is a general homeostatic response to
loss of reward, with one maladaptive consequence being increased behavioral responsiveness to drugs of
abuse and associated environments. It is further hypothesized that these consequences of reward loss can be
offset, in whole or part, by introducing alternative rewards. This is supported by preliminary data indicating that
environmental enrichment prevents the enhancing effect of food restriction on behavioral responsiveness to d-
amphetamine. The goal of proposed Aim 1 is therefore to test the prediction that transfer of food restricted rats to
an enriched environment prevents both the NAc synaptic incorporation of CP-AMPARs and increased
incentive effects of a cocaine-paired environment. Aim 2 tests the prediction that transfer of ad libitum fed rats
from an enriched to impoverished environment induces NAc synaptic incorporation of CP-AMPARs and
increases the incentive effects of a cocaine-paired environment in a manner that is dependent on CP-
AMPARs. The work proposed in this application has potential to benefit human health by providing insight into
the neurobiology of reward homeostasis and subversion of its mechanistic underpinnings by drugs and their
cues. More generally, results could shed new light on the nexus between environmental risk factors and the
biology of addiction.

## Key facts

- **NIH application ID:** 10448488
- **Project number:** 5R21DA053348-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Kenneth D Carr
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,688
- **Award type:** 5
- **Project period:** 2021-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448488

## Citation

> US National Institutes of Health, RePORTER application 10448488, Reward Homeostasis, Accumbens AMPA Receptor Trafficking and Drug Abuse (5R21DA053348-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10448488. Licensed CC0.

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