Fig. 3. Stimulation of DRN-NAc serotonin terminals and Pdyn^NAc cKO regulates cocaine preference.

A Cartoon showing DRN injection of AAV5-DIO-ChR2-EYFP and placement of optical cannula above the NAc in a SERT-Cre mouse. Below: expression of EYFP⁺ terminals in NAc of SERT-Cre mouse. B Schematic of cocaine CPP with pretreatment of KOR agonist and stimulation of serotonin terminals prior to cocaine conditioning. Prior to each cocaine conditioning session, mice were pretreated with KOR agonist (U50488; 5 mg/kg I.P.) and received concurrent optical stimulation of serotonin terminals in the NAc or control treatment. C Cocaine preference scores of mice receiving KOR agonist prior to cocaine conditioning with or without concurrent ChR2 stimulation of SERT⁺ terminals in the NAc (Dashed line shows typical unstressed cocaine preference) (n = 10–12). D Schematic of optical stimulation of SERT⁺ terminals in the NAc during rFSS. E Time immobile during swim bouts on day 2 of rFSS for mice with stimulation of NAc SERT terminals and controls (n = 6–7). F Time immobile during last swim bout of rFSS in E. G Representative images showing expression of retrogradely delivered fluorophore (EYFP) in the NAc of a Pdyn-Cre mouse. Scale bar = 200 µm. H Cartoon showing injection of virus delivering Cre-recombinase (AAV-Cre-EGFP) to the NAc of Pdyn-flx mice. Below: representative image showing expression of AAV-Cre-EGFP in the NAc. I Raw cocaine preference scores for control and Pdyn^NAc cKO mice with or without prior stress (n = 13–16).