Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat.
Veronica Serra, Liana Fattore, Maria Scherma, Roberto Collu, Maria Sabrina Spano, Walter Fratta, Paola Fadda
Psychopharmacology 2015 DOI: 10.1007/s00213-014-3641-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled behavioral and neurochemical study Peer reviewed |
|---|---|
| Population | Male Lister Hooded and Sprague-Dawley rats |
| Intervention | Salvinorin A |
| Dose | 0.5 or 1.0 μg/kg/infusion for self-administration; systemic doses of ≥40 μg/kg (LH rats) and ≥5 μg/kg (SD rats) for dopamine measurement |
| Duration | 20 days of self-administration sessions (2 h/day) |
| Topics | Salvia divinorum |
| Keywords | The drug Addiction addictive properties Compulsive self-administration Drug-seeking behavior Commonly abused substances Dopamine levels Hallucinogens salvinorin a |
| Citations | 26 |
| Key points | Salvinorin A increased dopamine in the nucleus accumbens shell but did not sustain stable intravenous self-administration in rats. |
Abstract
Salvinorin A is a recreational drug derived from Salvia divinorum, a sage species long used as an entheogen. While salvinorin A has potent hallucinogenic properties, its abuse potential has not been assessed consistently in controlled behavioural and neurochemical studies in rodents. This study aimed to assess salvinorin A abuse potential by measuring its capacity to establish and maintain self-administration behaviour and to modify dopamine (DA) levels in the nucleus accumbens (NAcc) of rats. Male Lister Hooded (LH) and Sprague-Dawley (SD) rats were allowed to self-administer salvinorin A (0.5 or 1.0 μg/kg/infusion) intravenously 2 h/day for 20 days under a continuous schedule of reinforcement and lever pressing as operandum. LH rats discriminated between the active and inactive levers but did not reach the acquisition criterion for stable self-administration (≥12 active responses vs ≤5 inactive responses for at least 5 consecutive days). SD rats discriminated between the two levers at the lower dose only but, like LH rats, never acquired stable self-administration behaviour. Systemic salvinorin A increased extracellular DA in the NAcc shell of both LH (at ≥40 μg/kg) and SD rats (at ≥5 μg/kg), but injection into the ventral tegmental area (VTA) induced no significant change in NAcc DA concentration in LH rats and only brief elevations in SD rats. Salvinorin A differs from other commonly abused compounds since although it affects accumbal dopamine transmission, yet it is unable, at least at the tested doses, to sustain stable intravenous self-administration behaviour.
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 7
- 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
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- Salvia divinorum: from recreational hallucinogenic use to analgesic and anti-inflammatory action. Journal of Pain Research 2019
- The translational potential of salvinorin A: systematic review and meta-analysis of preclinical studies. Translational Psychiatry October 10, 2025
- Salvia divinorum: un estudio fenomenológico y cognitivo de la experiencia en usuarios de Latinoamérica y España. Revista Iberoamericana ConCiencia April 9, 2022
and 2 more in the library
Cites 27
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- 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
- Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents British Journal of Pharmacology May 5, 2009
- Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology March 1, 2013
- Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Drug and Alcohol Dependence May 1, 2011
and 22 more in the library