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Research Articles, Behavioral/Cognitive

Prelimbic Cortex Activity during a Distress Tolerance Task Predicts Cocaine-Seeking Behavior in Male, But Not Female Rats

Travis M. Moschak, T. Joseph Sloand and Regina M. Carelli
Journal of Neuroscience 25 January 2023, 43 (4) 647-655; DOI: https://doi.org/10.1523/JNEUROSCI.1718-22.2022
Travis M. Moschak
1Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas 79902
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T. Joseph Sloand
2Department of Psychology & Neuroscience, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599
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Regina M. Carelli
2Department of Psychology & Neuroscience, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599
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Abstract

Distress tolerance (DT) is defined as the ability to persist in challenging goal-directed behavior in the face of stress, and individuals with low DT exhibit heightened drug-seeking behavior. However, no preclinical studies have examined the neurobiology underlying this phenomenon. To assess this, in vivo electrophysiology was used in Long Evans male and female rats during a DT task to record neural activity in the prelimbic cortex (PrL), a brain region implicated in drug-seeking. Rats were first assessed for DT, defined as the amount of time elapsed before rats quit seeking reward in an increasingly difficult operant task. Subsequently, rats underwent 2 weeks of self-administration for either water/saline or cocaine for 6 h/day. Animals then began a 1 month period of experimenter-imposed abstinence to induce heightened drug-seeking behavior. On day 28 of abstinence, DT and neural activity were reassessed; and on day 30, cocaine-seeking behavior was examined under extinction. Males had significantly higher DT than females and exhibited significantly more phasic PrL activity during the DT task. Furthermore, in male rats with a history of cocaine, PrL activity shifted to track DT; and this change in activity significantly correlated with the change in DT. Additionally, male (but not female) rats with low DT after 28 d of abstinence had significantly heightened drug-seeking behavior. Finally, PrL activity during the DT task predicted cocaine-seeking behavior. Collectively, these data demonstrate an important role for the PrL in DT in males, and link this neural activity and behavior to drug-seeking, particularly in males.

SIGNIFICANCE STATEMENT Distress tolerance (DT) is defined as the ability to persist in challenging goal-directed behavior in the face of stress, and individuals with low DT exhibit heightened drug-seeking. Here, we investigated the role of the prelimbic cortex (PrL) in DT and its relationship to cocaine-seeking in male and female rats. We found that males had significantly higher DT than females and exhibited significantly more PrL activity during the DT task. Furthermore, male (but not female) rats with low DT after 28 d of abstinence had significantly heightened drug-seeking behavior. Finally, PrL activity during the DT task predicted cocaine-seeking. These data demonstrate an important role for the PrL in DT and link this neural activity and behavior to drug-seeking in males.

  • addiction
  • behavior
  • cocaine
  • distress tolerance
  • prelimbic cortex
  • rats

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The Journal of Neuroscience: 43 (4)
Journal of Neuroscience
Vol. 43, Issue 4
25 Jan 2023
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Prelimbic Cortex Activity during a Distress Tolerance Task Predicts Cocaine-Seeking Behavior in Male, But Not Female Rats
Travis M. Moschak, T. Joseph Sloand, Regina M. Carelli
Journal of Neuroscience 25 January 2023, 43 (4) 647-655; DOI: 10.1523/JNEUROSCI.1718-22.2022

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Prelimbic Cortex Activity during a Distress Tolerance Task Predicts Cocaine-Seeking Behavior in Male, But Not Female Rats
Travis M. Moschak, T. Joseph Sloand, Regina M. Carelli
Journal of Neuroscience 25 January 2023, 43 (4) 647-655; DOI: 10.1523/JNEUROSCI.1718-22.2022
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Keywords

  • addiction
  • behavior
  • cocaine
  • distress tolerance
  • prelimbic cortex
  • rats

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