Effects of acute and repeated administration of salvinorin A on dopamine function in the rat dorsal striatum.
Brenda J Gehrke, Vladimir I Chefer, Toni S Shippenberg
Psychopharmacology April 2008 DOI: 10.1007/s00213-007-1067-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study using conventional and quantitative microdialysis Peer reviewed |
|---|---|
| Population | Rats (in vivo microdialysis and locomotor experiments) |
| Interventions | Salvinorin A Cocaine |
| Dose | 0; 20-200 nM (retrodialysis); 1.0 or 3.2 mg/kg per day x 5 days (i.p.); cocaine 20 mg/kg, i.p. |
| Duration | 5 days of repeated salvinorin A administration; cocaine challenge 48 h after repeated treatment |
| Topics | Salvia divinorum |
| Key findings | Acute intrastriatal salvinorin A produced a dose-related, kappa-opioid-receptor-reversible decrease in striatal dopamine that reflected reduced release rather than altered uptake. Repeated salvinorin A (1.0 or 3.2 mg/kg/day for 5 days) did not change basal dopamine or uptake, did not attenuate cocaine-induced locomotion, but did enhance cocaine-evoked dopamine overflow, suggesting its pharmacology differs from synthetic kappa-opioid agonists. |
Abstract
Acute systemic administration of salvinorin A, a naturally occurring kappa-opioid receptor (KOPr) agonist, decreases locomotion and striatal dopamine (DA) overflow. Conventional and quantitative microdialysis techniques were used to determine whether salvinorin A infusion into the dorsal striatum (DSTR) decreases DA overflow by altering DA uptake or release. The influence of repeated salvinorin A administration on basal DA dynamics and cocaine-evoked alterations in DA overflow and locomotion was also assessed. Salvinorin A was administered via the dialysis probe (0; 20-200 nM) or via intraperitoneal (i.p.) injection (1.0 or 3.2 mg/kg per day x 5 days). The effects of a challenge dose of cocaine were examined 48 h after repeated salvinorin treatment. Retrodialysis of salvinorin A produced a dose-related, KOPr antagonist reversible, decrease in DA levels. Extracellular DA levels were decreased whereas DA extraction fraction, which provides an estimate of DA uptake, was unaltered. In contrast to its acute administration, repeated salvinorin A administration did not modify dialysate DA levels. Similarly, neither basal extracellular DA levels nor DA uptake was altered. Unlike synthetic KOPr agonists, prior repeated administration of salvinorin A did not attenuate the locomotor activating effects of an acute cocaine (20 mg/kg, i.p.) challenge. However, cocaine-evoked DA overflow was enhanced. These data demonstrate that acute, but not repeated, salvinorin A administration decreases mesostriatal neurotransmission and that activation of DSTR KOPr is sufficient for this effect. Differences in the interaction of salvinorin and synthetic KOPr agonists with cocaine suggest that the pharmacology of these agents may differ.
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 25
- Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution Frontiers in Human Neuroscience May 23, 2017
- 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
- 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
- From local to global-fifty years of research on Salvia divinorum. Journal of Ethnopharmacology February 3, 2014
and 20 more in the library
Cites 9
- 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
- Salvinorin A: the "magic mint" hallucinogen finds a molecular target in the kappa opioid receptor. TIPS - Trends in Pharmacological Sciences March 1, 2003
- Salvia divinorum and the unique diterpene hallucinogen, Salvinorin (divinorin) A. Journal of Psychoactive Drugs 1994
and 4 more in the library