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Optogenetic inhibition of medial prefrontal cortex projections to the nucleus accumbens core and methyl supplementation via L‐Methionine attenuates cocaine‐primed reinstatement
Author(s) -
WRIGHT Katherine N.,
DOSSAT Amanda M.,
STRONG Caroline E.,
SAILER Lindsay L.,
PAVLOCK Samantha M.,
KABBAJ Mohamed
Publication year - 2018
Publication title -
integrative zoology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 34
ISSN - 1749-4877
DOI - 10.1111/1749-4877.12365
Subject(s) - optogenetics , nucleus accumbens , extinction (optical mineralogy) , self administration , prefrontal cortex , neuroscience , psychology , pharmacology , medicine , dopamine , chemistry , mineralogy , cognition
DNA methylation has been identified as a powerful and activity‐dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli, including exposure to drugs of abuse. Indeed, the medial prefrontal cortex (mPFC) projections to the nucleus accumbens (NAc) are critically important for reinstated cocaine‐seeking in a rodent model of cocaine relapse. This circuitry undergoes several epigenetic modifications following cocaine exposure, including changes in DNA methylation that are associated with drug‐seeking behavior. We have previously shown that methyl supplementation via L‐Methionine (MET) administration attenuates cocaine‐seeking behavior and reverses expression and methylation patterns of the immediate early gene c‐fos , suggesting that MET may act by altering the excitability of this circuitry during cocaine reinstatement. In the current study, male rats were microinjected with an adeno‐associated virus overexpressing halorhodopsin in the mPFC, optical fibers were surgically implanted into the NAc, and the rats were given injections of MET daily. Rats underwent acquisition of cocaine self‐administration (0.75 mg/kg/infusion, 2‐h sessions) followed by extinction training in the absence of drug‐paired cues. Two reinstatement tests were conducted: cue‐induced reinstatement without optogenetic manipulations and cocaine‐primed reinstatement with optogenetic inhibition of mPFC‐to‐NAc projections. There were no group differences before the cocaine‐primed reinstatement session, and all groups showed robust cue‐induced reinstatement. Both rats treated with MET and rats that received mPFC‐to‐NAc inhibition showed an abolishment of cocaine‐primed reinstatement, suggesting that systemic methyl supplementation may act through this critical circuity.