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Assessment of the kappa opioid agonist, salvinorin A, as a punisher of drug self-administration in monkeys

Abstract

Rationale

Drugs can function as punishers. However, work on the study of drugs as punishers is limited, as is the range of compounds known to function as punishers. Kappa opioid agonists, which have received much experimental attention as potential therapeutics for drug abuse, reportedly produce aversive effects. However, kappa agonists have yet to be tested as punishers of behavior.

Objective

The goal of the current study was to determine if a kappa agonist could function as a punisher of drug self-administration.

Method

In separate experiments, monkeys were allowed to choose in a two-lever choice design between intravenous injections of equal doses of either cocaine (0.1 mg/kg/injection on each lever) or remifentanil (0.1 μg/kg/injection on each lever) when one of the two options was mixed with various doses of the kappa agonist, salvinorin A.

Results

Choice for the cocaine and remifentanil options that were combined with salvinorin A decreased as a function of salvinorin A dose in all monkeys. However, operant response rates were not systematically affected by salvinorin A administration.

Conclusion

The present findings demonstrate that the kappa agonist, salvinorin A, can punish self-administration of a psychotimulant, cocaine, and a mu opioid, remifentanil. In consideration of these findings, it may be possible to curtail the abuse of some drugs by contingently delivering kappa agonists (e.g., as combination formularies for prescription medications).

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Acknowledgments

This research was supported by the National Institute on Drug Abuse grants DA019471 and DA026832 to WLW and DA018151 to TEP. The authors thank Steven Ross, Jacob Smith, and Sarah Smith for their expert technical assistance.

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Correspondence to Kevin B. Freeman.

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Freeman, K.B., Naylor, J.E., Prisinzano, T.E. et al. Assessment of the kappa opioid agonist, salvinorin A, as a punisher of drug self-administration in monkeys. Psychopharmacology 231, 2751–2758 (2014). https://doi.org/10.1007/s00213-014-3436-2

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Keywords

  • Cocaine
  • Remifentanil
  • Salvinorin A
  • Punishment
  • Kappa agonist
  • Monkey
  • Self-administration