# Nicotinic and Insular Cortical Mechanisms Contributing to Opiate Misuse

> **NIH NIH K01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $39,962

## Abstract

Project Summary/Abstract
Concurrent nicotine use is highly implicated in the propensity to misuse prescribed opiates, future development
of opiate dependence, and susceptibility to accidental opiate overdose. Approximately 83-95% of patients
involved in opioid treatment programs are tobacco users. As such, there exists a clear public health mandate
for elucidation of mechanisms contributing to opiate addiction liability resultant from opiate and nicotine
polysubstance use. The anterior insular cortex is heavily involved in processing the interoceptive stimulus
properties of commonly abused drugs and insular dysfunction is implicated in the development and
maintenance of substance use disorders. The role of the insular cortex in opiate addiction, and furthermore,
how nicotine may play a role, is currently underexplored. There is emerging evidence that nicotine interferes
with insular function, specifically through depressing synaptic potentiation and inhibiting the output of the
insular cortex. Preliminary data demonstrate that nicotine delivered to the anterior insular cortex interferes with
the processing of the stimulus properties of opiates in a quantitative manner, an effect remarkably similar to
insular chemogenetic inactivation. Specifically, subjects either administered nicotine or undergoing
chemogenetic inactivation of the insular cortex behave as if they have received a lower dose of morphine
relative to controls in paradigms examining both the reinforcing (conditioned place preference; CPP) and
aversive (conditioned taste avoidance; CTA) stimulus properties of opiates. As a result, tobacco smokers may
require more and stronger doses of opiates in order to achieve the desired effects. This reduced sensitivity to
the stimulus properties of opiates due to nicotine co-use may facilitate the development of opiate dependence.
The goal of this project is to elucidate the mechanisms and neural circuits through which insular cortical
nicotinic activity contributes to enhanced opiate addiction liability. These experiments will employ a
combination of psychophysical behavioral measures, site-specific behavioral pharmacology, circuit-specific
chemogenetic manipulation, and in vivo electrophysiology in order to fully characterize the mechanisms
through which insular cortical nicotinic activity may contribute to the development of opiate substance use
disorders. Furthermore, through completion of these proposed studies, the applicant will be competently
trained in new technical skills and perspectives, ultimately facilitating a successful transition to a principal
investigator conducting programmatic research on the comorbidity of nicotine and opiate abuse.

## Key facts

- **NIH application ID:** 11077005
- **Project number:** 3K01DA048336-05S1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Gregory Carl Loney
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $39,962
- **Award type:** 3
- **Project period:** 2024-05-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11077005

## Citation

> US National Institutes of Health, RePORTER application 11077005, Nicotinic and Insular Cortical Mechanisms Contributing to Opiate Misuse (3K01DA048336-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11077005. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*