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Am J Addict. 2017 Oct;26(7):751-759. doi: 10.1111/ajad.12607. Epub 2017 Aug 31.

Increased habenular connectivity in opioid users is associated with an α5 subunit nicotinic receptor genetic variant.

Author information

1
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas.
2
Michael E DeBakey VA Medical Center, Houston, Texas.
3
The Menninger Clinic, Houston, Texas.
4
University of Hawaii, Department of Psychology, Hilo, Hawaii.
5
Department of Neuroscience, Baylor College of Medicine, Houston, Texas.

Abstract

BACKGROUND AND OBJECTIVES:

Opioid use disorder (OUD) is a chronic disorder with relapse based on both desire for reinforcement (craving) and avoidance of withdrawal. The aversive aspect of dependence and relapse has been associated with a small brain structure called the habenula, which expresses large numbers of both opioid and nicotinic receptors. Additionally, opioid withdrawal symptoms can be induced in opioid-treated rodents by blocking not only opioid, but also nicotinic receptors. This receptor co-localization and cross-induction of withdrawal therefore might lead to genetic variation in the nicotinic receptor influencing development of human opioid dependence through its impact on the aversive components of opioid dependence.

METHODS:

We studied habenular resting state functional connectivity with related brain structures, specifically the striatum. We compared abstinent psychiatric patients who use opioids (N = 51) to psychiatric patients who do not (N = 254) to identify an endophenotype of opioid use that focused on withdrawal avoidance and aversion rather than the more commonly examined craving aspects of relapse.

RESULTS:

We found that habenula-striatal connectivity was stronger in opioid-using patients. Increased habenula-striatum connectivity was observed in opioid-using patients with the low risk rs16969968 GG genotype, but not in patients carrying the high risk AG or AA genotypes.

CONCLUSIONS:

We propose that increased habenula-striatum functional connectivity may be modulated by the nicotinic receptor variant rs16969968 and may lead to increased opioid use.

SCIENTIFIC SIGNIFICANCE:

Our data uncovered a promising brain target for development of novel anti-addiction therapies and may help the development of personalized therapies against opioid abuse. (Am J Addict 2017;26:751-759).

PMID:
28857330
PMCID:
PMC5745069
DOI:
10.1111/ajad.12607
[Indexed for MEDLINE]
Free PMC Article

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