Assessment of the kappa opioid agonist, salvinorin A, as a punisher of drug self-administration in monkeys.
Kevin B Freeman, Jennifer E Naylor, Thomas E Prisinzano, William L. Woolverton
Psychopharmacology July 1, 2014 DOI: 10.1007/s00213-014-3436-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental, within-subjects Peer reviewed |
|---|---|
| Population | Monkeys |
| Intervention | Salvinorin A |
| Topics | Salvia divinorum |
| Key findings | Salvinorin A punished self-administration of cocaine and remifentanil in monkeys, decreasing choice for the drug combined with the kappa agonist as its dose increased. |
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).
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
Citations in the library
Cited by 15
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders Frontiers in Pharmacology September 8, 2015
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- A unique natural selective kappa-opioid receptor agonist, salvinorin A, and its roles in human therapeutics. Phytochemistry May 1, 2017
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
and 10 more in the library
Cites 7
- Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Psychopharmacology May 1, 2005
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and salvinorin A on cocaine-induced drug-seeking in rats. Pharmacology, Biochemistry, and Behavior December 1, 2009
- Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans. Journal of Pharmacology and Experimental Therapeutics 2007
- Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens. Psychopharmacology April 7, 2010
and 2 more in the library