| First Author | Pomrenze MB | Year | 2022 |
| Journal | Neuron | Volume | 110 |
| Issue | 24 | Pages | 4125-4143.e6 |
| PubMed ID | 36202097 | Mgi Jnum | J:340912 |
| Mgi Id | MGI:7413835 | Doi | 10.1016/j.neuron.2022.09.024 |
| Citation | Pomrenze MB, et al. (2022) Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal. Neuron 110(24):4125-4143.e6 |
| abstractText | 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) sensor revealed that during withdrawal KORs block the NAc 5-HT release that normally occurs during social interactions. These results define a neuromodulatory mechanism that is engaged during protracted opioid withdrawal to induce maladaptive deficits in prosocial behaviors, which in humans contribute to relapse. |
