Staff and Researcher Publications
Language
English
Publication Date
10-1-2017
Journal
The American Journal on Addictions
DOI
10.1111/ajad.12607
PMID
28857330
PMCID
PMC5745069
PubMedCentral® Posted Date
10-1-2018
PubMedCentral® Full Text Version
Author MSS
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).
Keywords
Adult, Avoidance Learning, Connectome, Corpus Striatum, Female, Genetic Predisposition to Disease, Habenula, Humans, Magnetic Resonance Imaging, Male, Nerve Tissue Proteins, Opioid-Related Disorders, Receptors, Nicotinic, Substance Withdrawal Syndrome
Published Open-Access
yes
Recommended Citation
Curtis, Kaylah; Viswanath, Humsini; Velasquez, Kenia M; et al., "Increased Habenular Connectivity in Opioid Users Is Associated With an α5 Subunit Nicotinic Receptor Genetic Variant" (2017). Staff and Researcher Publications. 74.
https://digitalcommons.library.tmc.edu/clinic_pub/74
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