Striatal -opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect. Academic Article uri icon

abstract

  • 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 -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.

published proceedings

  • Cell Rep

altmetric score

  • 89.98

author list (cited authors)

  • Wang, W., Xie, X., Zhuang, X., Huang, Y., Tan, T., Gangal, H., ... Wang, J.

citation count

  • 2

complete list of authors

  • Wang, Wei||Xie, Xueyi||Zhuang, Xiaowen||Huang, Yufei||Tan, Tao||Gangal, Himanshu||Huang, Zhenbo||Purvines, William||Wang, Xuehua||Stefanov, Alexander||Chen, Ruifeng||Rodriggs, Lucas||Chaiprasert, Anita||Yu, Emily||Vierkant, Valerie||Hook, Michelle||Huang, Yun||Darcq, Emmanuel||Wang, Jun

publication date

  • February 2023