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A sex-dependent role for the prelimbic cortex in impulsive action both before and following early cocaine abstinence

Abstract

Although impulsive action is strongly associated with addiction, the neural underpinnings of this relationship and how they are influenced by sex have not been well characterized. Here, we used a titrating reaction time task to assess differences in impulsive action in male and female Long Evans rats both before and after short (4–6 days) or long (25–27 days) abstinence from 2 weeks of cocaine or water/saline self-administration (6 h daily access). Neural activity in the prelimbic cortex (PrL) and nucleus accumbens (NAc) core was assessed at each time point. We found that a history of cocaine self-administration increased impulsivity in all rats following short, but not long, abstinence. Furthermore, male rats with an increased ratio of excited to inhibited neurons in the PrL at the start of each trial in the task exhibited higher impulsivity in the naïve state (before self-administration). Following short abstinence from cocaine, PrL activity in males became more inhibited, and this change in activity predicted the shift in impulsivity. However, PrL activity did not track impulsivity in female rats. Additionally, although the NAc core tracked several aspects of behavior in the task, it did not track impulsivity in either sex. Together, these findings demonstrate a sex-dependent role for the PrL in impulsivity both before and after a history of cocaine.

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Fig. 1: Titrating reaction time task.
Fig. 2: Neural activity following the lever extension during the Naive TRTT test session.
Fig. 3: The relationship between neural activity following the lever extension and impulsivity.
Fig. 4: Cocaine self-administration and impulsivity.
Fig. 5: The change in neural activity following lever extension after abstinence from self-administration.

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Acknowledgements

We thank Joey Sloand, Caitlin Nygren, Iniya Muthukumaren, and Elijah Richardson for technical assistance.

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TMM and RMC were responsible for the study concept and design. TMM acquired the animal data. TMM and RMC assisted with data analysis and interpretation of findings. TMM drafted the manuscript. TMM and RMC provided critical revision of the manuscript for important intellectual content. All authors critically reviewed content and approved the final version for publication. All authors agree to be accountable for all aspects of the work to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Regina M. Carelli.

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Moschak, T.M., Carelli, R.M. A sex-dependent role for the prelimbic cortex in impulsive action both before and following early cocaine abstinence. Neuropsychopharmacol. 46, 1565–1573 (2021). https://doi.org/10.1038/s41386-021-01024-3

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