Salvinorin A modulates the neurotransmitters release from different mouse brain areas through presynaptic metabotropic receptors activation
Mario Marchi, Massimo Grilli, Elisa Neri, Stefania Zappettini, Mario Sessarego, Giovanni Romussi, Angela Bisio, Anna Pittaluga
Planta Medica July 1, 2008 DOI: 10.1055/s-0028-1084085 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental laboratory study Peer reviewed |
|---|---|
| Population | Isolated nerve terminals (synaptosomes) from mouse hippocampus, striatum, and prefrontal cortex |
| Intervention | Salvinorin-A |
| Topics | Salvia divinorum |
| Key findings | Salvinorin-A potentiated potassium-evoked noradrenaline release and inhibited potassium-evoked serotonin and dopamine release in a concentration-dependent manner, with effects prevented by Pertussis toxin, indicating involvement of G-protein coupled receptors. |
Abstract
Salvinorin-A is a component of Salvia divinorum , displaying psychoactive and hallucinogenic properties in humans. Recent literature suggests that this compound can act as a potent and selective opioid receptor agonist, having high affinity towards the K–opioid receptor subtype. The aim of our study was to investigate whether and to what extent this compound can alter the release of neurotransmitters from isolated nerve terminals (synaptosomes) prepared from mouse hippocampus (HC), striatum (STR) and prefrontal cortex (PFC). The experimental approach used, i.e. the up-down superfusion of a synaptosomal monolayer, is considered a method of choice to investigate presynaptic mechanisms of control of neurotransmitter release. We focused on the release of prelabelled [ 3 H]noradrenaline ([ 3 H]NA) and [ 3 H]serotonin ([ 3 H]5HT) from rat HC synaptosomes and of [ 3 H]dopamine ([ 3 H]DA) from PFC and STR synaptosomes. Salvinorin-A failed to affect the spontaneous release of all the three amines, but significantly modified the release of these neurotransmitters induced by transient (90s) exposure to 12 mM K + . In particular, Salvinorin-A potentiated in a concentration-dependent manner the K + -evoked release of [ 3 H]NA, while it inhibited, always in a concentration-dependent way the release of [ 3 H]5HT and of [ 3 H]DA. Both facilitation and inhibiton of amine exocytosis was prevented by entrapping into synaptosomes the Pertussis toxin, suggesting the primary involvement in these effects of G-protein coupled receptors sensitive to this toxin. These results may be relevant to the comprehension of the molecular mechanisms involved in the central effects induced by this natural product.
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 |