Striatal μ-opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect.
Fiche publication
Date publication
février 2023
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DARCQ Emmanuel
Tous les auteurs :
Wang W, Xie X, Zhuang X, Huang Y, Tan T, Gangal H, Huang Z, Purvines W, Wang X, Stefanov A, Chen R, Rodriggs L, Chaiprasert A, Yu E, Vierkant V, Hook M, Huang Y, Darcq E, Wang J
Lien Pubmed
Résumé
Withdrawal from chronic opioid use often causes hypodopaminergic states and negative affect, which may drive relapse. Direct-pathway medium spiny neurons (dMSNs) in the striatal patch compartment contain μ-opioid receptors (MORs). It remains unclear how chronic opioid exposure and withdrawal impact these MOR-expressing dMSNs and their outputs. Here, we report that MOR activation acutely suppressed GABAergic striatopallidal transmission in habenula-projecting globus pallidus neurons. Notably, withdrawal from repeated morphine or fentanyl administration potentiated this GABAergic transmission. Furthermore, intravenous fentanyl self-administration enhanced GABAergic striatonigral transmission and reduced midbrain dopaminergic activity. Fentanyl-activated striatal neurons mediated contextual memory retrieval required for conditioned place preference tests. Importantly, chemogenetic inhibition of striatal MOR neurons rescued fentanyl withdrawal-induced physical symptoms and anxiety-like behaviors. These data suggest that chronic opioid use triggers GABAergic striatopallidal and striatonigral plasticity to induce a hypodopaminergic state, which may promote negative emotions and relapse.
Mots clés
CP: Neuroscience, direct-pathway medium spiny neurons, dMSNs, dopaminergic neurons, fentanyl, habenula-projecting globus pallidus neurons, GPh, morphine, negative emotional state, striatum, striosome and matrix compartments, substantia nigra pars compacta, SNc, μ-opioid receptor, MOR
Référence
Cell Rep. 2023 02 28;42(2):112089