A multivariate regressor of patterned dopamine release predicts relapse to cocaine

Author(s)

Lujan, Miguel A. ; Oliver, Brandon L. ; Young-Morrison, Reana ; Engi, Sheila A. ; Zhang, Lan-Yuan ; Wenzel, Jennifer M. ; Li, Yulong ; Zlebnik, Natalie E. ; Cheer, Joseph F.

• Document type: Journal article
• Source: CELL REPORTS; v. 42, n. 6, p. 17-pg., 2023-06-27.

Abstract

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 dopa-mine 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. (AU)

• FAPESP's process: 19/23286-3 - Effects of adolescent cannabinoid exposure on the development of mesocorticolimbic dopamine circuitry
• Grantee: Sheila Antonagi Engi
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor