Sex-Dependent Genetic Expression Signatures within Cocaine- and Sucrose-Seeking Ensembles in Mice

Litif, C. G.; Flom, L. T.; Sandum, K. L.; Hodgins, S. L.; Vaccaro, L.; Stitzel, J. A.; Blouin, N. A.; Mannino, M. C.; Gigley, J. P.; Schoborg, T.; Bobadilla, A.-C.

doi:10.1101/2023.11.02.565378

bioRxiv · 10.1101/2023.11.02.565378

Sex-Dependent Genetic Expression Signatures within Cocaine- and Sucrose-Seeking Ensembles in Mice

Litif, C. G.·Flom, L. T.·Sandum, K. L.·Hodgins, S. L.·Vaccaro, L.·Stitzel, J. A.·Blouin, N. A.·Mannino, M. C.·Gigley, J. P.·Schoborg, T.·Bobadilla, A.-C.

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Abstract

Maladaptive reward seeking is a hallmark of cocaine use disorder. To develop therapeutic targets, it is critical to understand the neurobiological changes specific to cocaine-seeking without altering the seeking of natural rewards, e.g., sucrose. The prefrontal cortex (PFC) and the nucleus accumbens core (NAcore) are known regions associated with cocaine- and sucrose-seeking ensembles, i.e., a sparse population of co-activated neurons. Within ensembles, transcriptomic alterations in the PFC and NAcore underlie the learning and persistence of cocaine- and sucrose-seeking behavior. However, transcriptomes exclusively driving cocaine seeking independent from sucrose seeking have not yet been defined using a within-subject approach. Using Ai14:cFos-TRAP2 transgenic mice in a dual cocaine and sucrose self-administration model, we fluorescently sorted (FACS) and characterized (RNAseq) the transcriptomes defining cocaine- and sucrose-seeking ensembles. We found reward- and region-specific transcriptomic changes that will help develop clinically relevant genetic approaches to decrease cocaine-seeking behavior without altering non-drug reward-based positive reinforcement.

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Litif, C. G., Flom, L. T., Sandum, K. L., Hodgins, S. L., Vaccaro, L., Stitzel, J. A., Blouin, N. A., Mannino, M. C., Gigley, J. P., Schoborg, T., Bobadilla, A.-C.. 2023-11-05. Sex-Dependent Genetic Expression Signatures within Cocaine- and Sucrose-Seeking Ensembles in Mice. https://doi.org/10.1101/2023.11.02.565378

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