Metabolic changes in the rodent brain after acute administration of salvinorin A.
Jacob M Hooker, Vinal Patel, Shiva Kothari, Wynne K Schiffer
Molecular imaging and biology 2009 DOI: 10.1007/s11307-008-0192-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult male rats |
| Intervention | Salvinorin A |
| Measures | FDG uptake, locomotor activity |
| Topics | Salvia divinorum |
| Key findings | Salvinorin A increased FDG uptake in several brain regions associated with kappa-opioid receptors, including the periaqueductal grey, bed nucleus of the stria terminalis, cerebellar vermis, and hypothalamus, as well as in auditory, sensory, and frontal cortices, while decreasing uptake in the dorsolateral striatum and hippocampus. Locomotor activity did not differ between treated and control rats. |
Abstract
Salvinorin A (SA) is a potent and highly selective kappa-opioid receptor (KOR) agonist with rapid kinetics and commensurate behavioral effects; however, brain regions associated with these effects have not been determined. Freely moving adult male rats were given SA intraperitoneally during uptake and trapping of the brain metabolic radiotracer, 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG), followed by image acquisition in a dedicated animal positron emission tomography (PET) system. Age-matched control animals received vehicle treatment. Animal behavior during FDG uptake was recorded digitally and later analyzed for locomotion. Group differences in regional FDG uptake normalized to whole brain were determined using Statistical Parametric Mapping (SPM) and verified by region of interest (ROI) analysis. SA-treated animals demonstrated significant increases in FDG uptake compared to controls in several brain regions associated with the distribution of KOR such as the periaqueductal grey, bed nucleus of the stria terminalis and the cerebellar vermis, as well as in the hypothalamus. Significant bilateral activations were also observed in the auditory, sensory, and frontal cortices. Regional decreases in metabolic demand were observed bilaterally in the dorsolateral striatum and hippocampus. Locomotor activity did not differ between SA and vehicle during FDG uptake. We have provided the first extensive maps of cerebral metabolic activation due to the potent kappa-opioid agonist, salvinorin A. A major finding from our small animal PET studies using FDG was that neural circuits affected by SA may not be limited to direct activation or inhibition of kappa-receptor-expressing cells. Instead, salvinorin A may trigger brain circuits that mediate the effects of the drug on cognition, mood, fear and anxiety, and motor output.
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 12
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- Salvia divinorum: from Mazatec medicinal and hallucinogenic plant to emerging recreational drug. Human Psychopharmacology: Clinical and Experimental September 1, 2013
- Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action. Journal of Pain Research 2019
- Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans The International Journal of Neuropsychopharmacology February 12, 2016
- Neuropathic and inflammatory antinociceptive effects and electrocortical changes produced by Salvia divinorum in rats. Journal of Ethnopharmacology July 12, 2017
and 7 more in the library
Cites 18
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Opioid receptors and legal highs:Salvia divinorumand Kratom Clinical Toxicology 2008
- 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
- Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Biological Psychiatry February 1, 2008
- Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans. Neuroimage July 1, 2008
and 13 more in the library