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Hippocampal mu opioid receptors are modulated following cocaine self‐administration in rat
Author(s) -
De Sa Nogueira David,
Bourdy Romain,
Filliol Dominique,
Romieu Pascal,
Befort Katia
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.15217
Subject(s) - neurochemical , addiction , opioid , μ opioid receptor , h3k4me3 , pharmacology , neuroscience , brain stimulation reward , self administration , opioid receptor , chromatin immunoprecipitation , receptor , epigenetics , medicine , psychology , chemistry , gene expression , nucleus accumbens , promoter , gene , biochemistry
Cocaine addiction is a complex pathology induced by long‐term brain changes. Understanding the neurochemical changes underlying the reinforcing effects of this drug of abuse is critical for reducing the societal burden of drug addiction. The mu opioid receptor plays a major role in drug reward. This receptor is modulated by chronic cocaine treatment in specific brain structures, but few studies investigated neurochemical adaptations induced by voluntary cocaine intake. In this study, we investigated whether intravenous cocaine‐self administration (0.33 mg/kg/injection, fixed‐ratio 1 [FR1], 10 days) in rats induces transcriptional and functional changes of the mu opioid receptor in reward‐related brain regions. Epigenetic processes with histone modifications were examined for two activating marks, H3K4Me3, and H3K27Ac. We found an increase of mu opioid receptor gene expression along with a potentiation of its functionality in hippocampus of cocaine self‐administering animals compared to saline controls. Chromatin immunoprecipitation followed by qPCR revealed no modifications of the histone mark H3K4Me3 and H3K27Ac levels at mu opioid receptor promoter. Our study highlights the hippocampus as an important target to further investigate neuroadaptive processes leading to cocaine addiction.