A multivariate regressor of patterned dopamine release predicts relapse to cocaine
Miguel Á. Luján,
Brandon L. Oliver,
Reana Young-Morrison,
Sheila A. Engi,
Lan-Yuan Zhang,
Jennifer M. Wenzel,
Yulong Li,
Natalie E. Zlebnik,
Joseph F. Cheer
Affiliations
Miguel Á. Luján
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
Brandon L. Oliver
Division of Biomedical Sciences, University of California Riverside, School of Medicine, Riverside, CA, USA
Reana Young-Morrison
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
Sheila A. Engi
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
Lan-Yuan Zhang
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
Jennifer M. Wenzel
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
Yulong Li
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China; PKU-IDG/McGovern Institute for Brain Research, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China
Natalie E. Zlebnik
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Division of Biomedical Sciences, University of California Riverside, School of Medicine, Riverside, CA, USA; Corresponding author
Joseph F. Cheer
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; Corresponding author
Summary: Understanding mesolimbic dopamine adaptations underlying vulnerability to drug relapse is essential to inform prognostic tools for effective treatment strategies. However, technical limitations have hindered the direct measurement of sub-second dopamine release in vivo for prolonged periods of time, making it difficult to gauge the weight that these dopamine abnormalities have in determining future relapse incidence. Here, we use the fluorescent sensor GrabDA to record, with millisecond resolution, every single cocaine-evoked dopamine transient in the nucleus accumbens (NAc) of freely moving mice during self-administration. We reveal low-dimensional features of patterned dopamine release that are strong predictors of cue-induced reinstatement of cocaine seeking. Additionally, we report sex-specific differences in cocaine-related dopamine responses related to a greater resistance to extinction in males compared with females. These findings provide important insights into the sufficiency of NAc dopamine signaling dynamics—in interaction with sex—for recapitulating persistent cocaine seeking and future relapse vulnerability.
