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. 2021 May;53(10):3341-3349.
doi: 10.1111/ejn.15217. Epub 2021 Apr 16.

Hippocampal mu opioid receptors are modulated following cocaine self-administration in rat

David De Sa Nogueira  1 , Romain Bourdy  1 , Dominique Filliol  1 , Pascal Romieu  1 , Katia Befort  1
Affiliations

Hippocampal mu opioid receptors are modulated following cocaine self-administration in rat

David De Sa Nogueira et al. Eur J Neurosci. 2021 May.

Abstract

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.

Keywords: cocaine; epigenetics; gene expression; hippocampus; mu opioid receptor.

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