Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal.

ABSTRACT: Social isolation during opioid withdrawal is a major contributor to the current opioid addiction crisis. We find that sociability deficits during protracted opioid withdrawal in mice require activation of kappa opioid receptors (KORs) in the nucleus accumbens (NAc) medial shell. Blockade of release from dynorphin (Pdyn)-expressing dorsal raphe neurons (DR^Pdyn), but not from NAc^Pdyn neurons, prevents these deficits in prosocial behaviors. Conversely, optogenetic activation of DR^Pdyn neurons reproduced NAc KOR-dependent decreases in sociability. Deletion of KORs from serotonin (5-HT) neurons, but not from NAc neurons or dopamine (DA) neurons, prevented sociability deficits during withdrawal. Finally, measurements with the genetically encoded GRAB_5-HT

SUBMITTER: Pomrenze MB 

PROVIDER: S-EPMC9789200 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature