Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats.
Lisa E Baker, John J Panos, Bryan A Killinger, Mary M Peet, Lisa M Bell, Larissa A Haliw, Sheryl L Walker
Psychopharmacology April 1, 2009 DOI: 10.1007/s00213-008-1458-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment with drug discrimination training Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Male Sprague-Dawley rats |
| Interventions | Salvinorin A U69 593 U50 488 salvinorin B ethoxymethyl ether salvinorin B methoxymethyl ether |
| Dose | 0.125-3.0 mg/kg (salvinorin A), 0.13 mg/kg (U69,593), 3.0 mg/kg (U50,488), 0.005-0.10 mg/kg (salvinorin B ethoxymethyl ether), 0.03-0.10 mg/kg (salvinorin B methoxymethyl ether) |
| Topics | Addiction Salvia divinorum |
| Keywords | Plant compound Synthetic cousins Derivatives Therapeutic potential Mood disorders Treating New therapeutic options Medicinal applications Kappa receptors Brain receptors Receptor interaction Neuropharmacology Mechanism of action Sensory cues Preclinical research Animal studies Trained rats Experiments Drug screening Experimental models |
| Citations | 57 |
| Key findings | Salvinorin A and two synthetic derivatives of salvinorin B fully substituted for kappa opioid agonists U69,593 and U50,488 in drug discrimination tests, confirming that salvinorin A's discriminative stimulus effects are mediated by kappa receptors. |
Abstract
Research interests regarding the psychopharmacology of salvinorin A have been motivated by the recreational use and widespread media focus on the hallucinogenic plant, Salvia divinorum. Additionally, kappa opioid (KOP) receptor ligands may have therapeutic potential in the treatment of some neuropsychiatric conditions, including drug dependence and mood disorders. Salvinorin A is a selective KOP agonist, but only a few studies have explored the discriminative stimulus effects of this compound. This study compared the discriminative stimulus effects of salvinorin A and two synthetic derivatives of salvinorin B to the KOP agonists, U69,593 and U50,488. Sixteen male Sprague-Dawley rats trained to discriminate U69,593 (0.13 mg/kg, s.c., N = 8) or U50,488 (3.0 mg/kg, i.p., N = 8) under a fixed-ratio 20 schedule of food reinforcement were administered substitution tests with salvinorin A (0.125-3.0 mg/kg, i.p.). The animals trained to discriminate U69,593 were also administered substitution tests with salvinorin B ethoxymethyl ether (0.005-0.10 mg/kg, i.p.) and salvinorin B methoxymethyl ether (0.03-0.10 mg/kg, i.p.). Another eight rats were trained to discriminate 2.0 mg/kg salvinorin A and tested with U69,593 (0.04-0.32 mg/kg) and U50,488 (0.4-3.2 mg/kg). Salvinorin A and both synthetic derivatives of salvinorin B substituted completely for U69,593. Additionally, cross-generalization was observed between salvinorin A and both KOP agonists. These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors. Future studies may assist in the development and screening of salvinorin A analogs for potential pharmacotherapy.
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 30
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Psychopharmacology June 1, 2010
- 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
- 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
- Acute and post-acute behavioral and psychological effects of salvinorin A in humans. Psychopharmacology March 1, 2012
and 25 more in the library
Cites 21
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- 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
- Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum The Journal of Organic Chemistry November 1, 1984
- Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). Journal of Ethnopharmacology May 1, 1983
and 16 more in the library