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

A kappa opioid agonist, salvinorin A, can punish self-administration of cocaine and remifentanil in monkeys. In a two-lever choice design, monkeys chose between equal doses of cocaine or remifentanil, with one option mixed with varying doses of salvinorin A. Choice for the drug combined with salvinorin A decreased as its dose increased, while operant response rates were unaffected. The findings suggest that kappa agonists may have potential to curtail drug abuse when delivered contingently, such as in combination formularies for prescription medications.

Study at a glance

Abstract

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