Increased habenular connectivity in opioid users is associated with an ?5 subunit nicotinic receptor genetic variant.

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).

SUBMITTER: Curtis K 

PROVIDER: S-EPMC5745069 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature