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Acute pain-related depression of operant responding maintained by social interaction or food in male and female rats

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Abstract

Rationale

Clinically relevant pain is often associated with functional impairment and behavioral depression, including depression of social behavior. Moreover, recovery of function is a major goal in pain treatment. We used a recently developed model of operant responding for social interaction in rats to evaluate the vulnerability of social behavior to an experimental pain manipulation and the sensitivity of pain-depressed social behavior to treatment with clinically effective analgesics.

Methods

Sprague–Dawley male and female rats were trained to lever press for social access to another rat, and responding was evaluated after treatment with (a) intraperitoneal injection of dilute lactic acid (IP acid; 0.18–5.6%) administered alone as a visceral noxious stimulus, (b) the mu-opioid receptor (MOR) agonist morphine (0.32–10 mg/kg) or nonsteroidal anti-inflammatory drug (NSAID) ketoprofen (10 mg/kg) administered alone, or (c) morphine or ketoprofen administered before IP acid. For comparison, the same treatments were evaluated in separate rats trained to lever press for food delivery.

Results

Both IP acid alone and morphine alone more potently decreased responding maintained by social interaction than by food, whereas ketoprofen did not affect responding for either reinforcer. In general, analgesics were most effective to rescue operant responding when relatively low IP acid concentrations produced significant but submaximal behavioral depression; however, morphine was not effective to rescue responding for social interaction.

Conclusions

Operant responding maintained by social interaction was more sensitive to pain-related disruption and less responsive to opioid analgesic rescue than food-maintained operant responding. Social behavior may be especially vulnerable to depression by pain states.

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Funding

This work was supported by NIDA-NIH grants P30-DA033934 and R00-DA047976 and by the Intramural Research Program of NIDA-NIH.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA

    A. N. Baldwin, M. L. Banks, S. A. Marsh, E. A. Townsend & S. Stevens Negus

  2. Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute On Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    Y. Shaham

  3. Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA

    M. Venniro

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  1. A. N. Baldwin
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  2. M. L. Banks
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  3. S. A. Marsh
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Correspondence to S. Stevens Negus.

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Baldwin, A.N., Banks, M.L., Marsh, S.A. et al. Acute pain-related depression of operant responding maintained by social interaction or food in male and female rats. Psychopharmacology 239, 561–572 (2022). https://doi.org/10.1007/s00213-021-06048-7

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  • DOI: https://doi.org/10.1007/s00213-021-06048-7

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