Exposure to the selective kappa-opioid receptor agonist salvinorin A modulates the behavioral and molecular effects of cocaine in rats.
Elena H Chartoff, David Potter, Diane Damez-Werno, Bruce M Cohen, William A Carlezon
Neuropsychopharmacology October 2008 DOI: 10.1038/sj.npp.1301659 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Salvinorin A Cocaine SKF 82958 |
| Measures | c-Fos expression, locomotor activity |
| Topics | Salvia divinorum |
| Key findings | Acute SalvA blocked cocaine-induced locomotor activity and c-Fos expression, whereas repeated SalvA in activity chambers potentiated these responses, but not when given in home cages. Acute SalvA also blocked the locomotor effects of a D1 agonist, indicating interaction with D1 receptor signaling. |
Abstract
Stress and chronic exposure to drugs of abuse can trigger addictive and depressive disorders. Both stimuli increase activity of dynorphin, a neuropeptide that acts at kappa-opioid receptors (KORs). In humans, KOR agonists cause dysphoria, raising the possibility that dynorphin modulates the depressive-like effects of stress and chronic drug use. We examined if KOR activation alters sensitivity to stimulant drugs by assessing the effects of the selective KOR agonist, salvinorin A (SalvA), on cocaine-induced locomotor activity and c-Fos expression. Acute administration of SalvA blocked the locomotor-stimulant effects of cocaine, whereas repeated SalvA together with concomitant exposure to activity testing chambers potentiated the locomotor response to a cocaine challenge. In contrast, repeated SalvA administered in home cages rather than the activity chambers failed to potentiate the locomotor response to a cocaine challenge. One potential explanation for these findings is that activation of KORs disrupts context conditioning: acute locomotor responses to SalvA alone did not fully habituate with repeated testing in the activity chambers. The effects of SalvA on locomotor activity paralleled its effects on cocaine-induced c-Fos expression in the dorsal striatum: acute SalvA attenuated cocaine-induced c-Fos, whereas repeated SalvA potentiated it when administered in the activity chambers but not the home cage. Acute SalvA also blocked the locomotor stimulant effects of the D1 receptor agonist SKF 82958, whereas repeated SalvA potentiated these effects when administered in the activity chambers. These findings suggest that SalvA regulates the stimulant effects of cocaine through interactions with D1 receptor-mediated signaling in the dorsal striatum.
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 29
- 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
- Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo. Journal of Molecular Medicine September 1, 2011
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A. Journal of Natural Products April 25, 2011
and 24 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: a novel and highly selective kappa-opioid receptor agonist. Life Sciences October 15, 2004
- Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. Journal of Pharmacology and Experimental Therapeutics January 2006
and 4 more in the library