# ROLE OF OREXIN IN COCAINE DEMAND AND ADDICTION

> **NIH NIH R01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2022 · $527,495

## Abstract

Project Summary/Abstract
A large number of studies over the last 14 years show that orexin neurons play an important role in reward
processing and drug abuse. Although these studies show that orexin-1 receptor (OxR1) signaling is particularly
involved in the motivation for many drugs of abuse, none have linked this system to the persistent, chronically
relapsing nature of addiction. Here, we extend studies from the previous terms of this project to tackle this
important issue. We recently found that the intermittent access (IntA) cocaine self-administration paradigm
produces a strong, multiphenotype addiction-like state as well as increased numbers of orexin-expressing
neurons. Importantly we find that the IntA-induced increase in addiction behaviors and orexin expression are
persistent (>30d of abstinence). We also find that chronic administration of an OxR1 antagonist during IntA
blocks the increased demand that this paradigm normally produces. Here, we propose to more fully characterize
the IntA-linked addiction profile and induced-orexin neurons following 30d abstinence. We also will examine the
contribution of OxR1 and OxR2 signaling in ventral tegmental area (VTA) and paraventricular thalamus (PVT),
two reward-related areas previously linked to orexin function, in persistent addiction behaviors after IntA. Finally,
we will test whether the FDA-approved dual orexin receptor antagonist, Belsomra™ (suvorexant), is effective in
acutely decreasing addiction behaviors, and in preventing the transition from a moderate to a severe addiction
profile. Together, the proposed experiments are a natural and important extension of the prior studies in this
project and will represent an important step forward in the development of an orexin-based treatment for cocaine
addiction.

## Key facts

- **NIH application ID:** 10299632
- **Project number:** 5R01DA006214-32
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Gary S. Aston-Jones
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $527,495
- **Award type:** 5
- **Project period:** 1992-08-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299632

## Citation

> US National Institutes of Health, RePORTER application 10299632, ROLE OF OREXIN IN COCAINE DEMAND AND ADDICTION (5R01DA006214-32). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10299632. Licensed CC0.

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