# Interoceptive processing and alcohol relapse-like behavior

> **NIH NIH F32** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $73,062

## Abstract

Abstract
Stimuli associated with drugs have a powerful influence over the behavior. Many studies have established the
ability of drug-related cues and contexts to induce relapse after a period of abstinence. Importantly, exposure
to drug-associated cues can also produce specific interoceptive effects related to drug craving, such as
feelings of increased tension, jitteriness, and changes in heart rate. However few studies have examined how
interoceptive responses to these cues can then become drivers of behavior. The current experiments propose
to use a highly relevant behavioral model of context-induced reinstatement combined with manipulation of
neural circuitry likely to be involved in interoceptive perception using viral chemogenetic technology. In these
experiments, rats will be trained to self-administer alcohol in a specific context that will become associated with
the drug. Subsequently, rats will undergo extinction in a separate context where responses do not result in
delivery of alcohol. Then, rats will be tested in the original alcohol-associated context in a two-phase
reinstatement procedure consisting of a seeking phase where lever presses have no programmed
consequence (i.e., seeking phase) and then a re-initiation of self-administration phase where responses will
again be rewarded (i.e., re-initiation of self-administration phase). This design allows for examination of
multiple factors that can contribute to relapse. Using this design, Aim 1 will determine the functional role of the
nucleus reuniens (RE) to anterior insula (AI) projection with virus infusions of Gi-coupled hM4Di Designer
Receptors Exclusively Activated by Designer Drugs (DREADDs) into the RE followed by implantation of
bilateral cannulae targeting the AI. This circuit will be silenced on the reinstatement test day by activating the
Gi DREADDs via delivery of the ligand clozapine-N-oxide (CNO) into the AI. I hypothesize that silencing this
circuit will disrupt processing of interoceptive cues that contribute to alcohol seeking and will increase
responding upon re-initiation of self-administration. Aim 2 will use the same viral strategy to silence the
projection from the nucleus of the solitary tract (NTS) to the RE. I hypothesize that Gi DREADD activation in
this circuit will both disrupt interoceptive cues that contribute to alcohol seeking behavior and re-initiation of
alcohol self-administration. Altogether, the experiments in this application seek to demonstrate that silencing of
brain circuits likely to be involved in the processing of peripheral body state information disrupts use of this
information as an interoceptive cue that contributes to alcohol use disorder and relapse.

## Key facts

- **NIH application ID:** 10313766
- **Project number:** 1F32AA029289-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Dennis Lovelock
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $73,062
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313766

## Citation

> US National Institutes of Health, RePORTER application 10313766, Interoceptive processing and alcohol relapse-like behavior (1F32AA029289-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10313766. Licensed CC0.

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