Cardiovascular and Renal Responses Produced by the Central Microinjection of Salvinorin A in Ketamine/Xylaxine‐Anesthetized Rats
Helmut B Gottlieb, Lisa Ji, JT Cunningham
The FASEB Journal April 1, 2009 DOI: 10.1096/fasebj.23.1_supplement.1015.8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Anesthetized Sprague-Dawley rats with chronic arterial, venous, and bladder cannulas |
| Interventions | Salvinorin A Vehicle (DMSO) |
| Dose | 10 nmol or 30 nmol |
| Duration | 80 minutes of urine collection after injection, in 10-minute periods |
| Topics | Esketamine Ketamine Salvia divinorum |
| Key findings | Intracerebroventricular Salvinorin A (10 or 30 nmol) markedly increased urine flow without significantly changing urinary sodium excretion or blood pressure. The authors conclude that Salvinorin A's renal effects differ from those of the central kappa agonist U-50488H, which affects both urine flow and sodium excretion. |
Abstract
One of active ingredients of Salvia divinorum , Salvinorin A (Sal A), has been shown to be a kappa opioid receptor agonist. The activation of central kappa opioid systems markedly affects renal function (water diuresis) in a manner that is different from any clinically used diuretic to date. The cardiovascular and renal effects produced by central administration of Salvinorin A are yet to be determined.
Methods: Sprague‐Dawley rats were implanted with chronic arterial, venous and bladder cannulas and infused with isotonic saline (55 ml/min, iv) containing ketamine (1 mg/Kg/min) and xylazine (80 mg/Kg/min). After equilibration, urine was collected during two control periods (C, 10‐min ea) and immediately after ICV Salvinorin A (10 nmol or 30 nmol) for 80 min (10‐min ea). Controls received injections of vehicle (DMSO) into the lateral ventricle (n=6).
Results: ICV injection of Salvinorin A markedly increased V without significantly changing UNaV or blood pressure.
Conclusion: In anesthetized rats, Salvinorin A selectively affected urine output (diuresis), whereas the activation of central kappa receptors U‐50488H affects both urine flow and UNaV. From these studies, it is apparent that Salvinorin A's effects on renal differ from those elicited by central kappa agonists (endogenous and synthetic). Supported by HL62579 and NIH EARDA grant.
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 |