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Investigating individual differences in opioid-taking and opioid-seeking behavior in male rats

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Abstract

Rationale

Understanding the behavioral and neurobiological factors that render some individuals more susceptible than others to opioid addiction will be critical in combatting the opioid crisis.

Objective

The purpose of the current study was to determine if behavioral traits associated with an increased likelihood to take and seek cocaine are the same traits that render one more susceptible to opioid-taking and opioid-seeking behavior. Individual differences in the acquisition of remifentanil self-administration and subsequent cue-induced reinstatement of remifentanil-seeking behavior were investigated using two animal models: the high-responder (HR)/low-responder (LR) and sign-tracker (ST)/goal-tracker (GT) models. Relative to LR rats, HR rats show increased novelty-induced locomotion or “sensation-seeking” behavior, and are more likely to acquire cocaine-taking behavior and do so at a faster rate. Relative to GT rats, ST rats attribute greater incentive motivational value to reward cues and are more likely to exhibit reinstatement of cocaine-seeking behavior.

Results

In contrast to previous work using cocaine, we did not observe individual differences with respect to the acquisition of remifentanil self-administration- or cue-induced reinstatement of remifentanil-seeking behavior within the context of either the HR/LR or ST/GT model. Thus, neither the sensation-seeking trait nor the propensity to attribute incentive motivational value to reward cues predicts remifentanil-taking or remifentanil-seeking behavior.

Conclusions

These findings suggest that different traits may confer the initiation of opioid- vs. cocaine-taking behavior, and the propensity to relapse to opioid- vs. cocaine-seeking. Additional studies are needed to identify which neurobehavioral constructs confer liability to opioid use and relapse.

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Acknowledgements

We would like to thank Dr. Paolo Campus for assistance with figures, Allison Johnson and Hannah Davies for assistance with jugular catheterization surgeries, and Maurice Chojecki for technical support. We would also like to thank Drs. Terry Robinson and Sara Westbrook for helpful comments on previous versions of this manuscript.

Funding

This work was supported by the National Institute on Drug Abuse branch of the National Institutes of Health (R01-DA038599-04S2) awarded to Dr. Shelly B Flagel.

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Authors and Affiliations

  1. Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA

    Stephen E. Chang & Shelly B. Flagel

  2. Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI, USA

    Lauren D. Krueger

  3. Office of Comparative Medicine, University of Utah, Salt Lake City, UT, USA

    Lauren D. Krueger

  4. Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA

    Shelly B. Flagel

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  1. Stephen E. Chang
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  2. Lauren D. Krueger
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Correspondence to Shelly B. Flagel.

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Chang, S.E., Krueger, L.D. & Flagel, S.B. Investigating individual differences in opioid-taking and opioid-seeking behavior in male rats. Psychopharmacology 239, 1065–1080 (2022). https://doi.org/10.1007/s00213-021-06023-2

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