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Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2006 Jan; Vol. 316 (1), pp. 440-7. Date of Electronic Publication: 2005 Oct 13. - Publication Year :
- 2006
-
Abstract
- Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of kappa-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A (SalvA), a potent and highly selective kappa-opioid agonist, would produce depressive-like effects in the forced swim test (FST) and intracranial self-stimulation (ICSS) test, which are behavioral models often used to study depression in rats. We extracted, isolated, and purified SalvA from Salvia divinorum plant leaves and examined its effects on behavior in the FST and ICSS test across a range of doses (0.125-2.0 mg/kg) after systemic (intraperitoneal) administration. SalvA dose dependently increased immobility in the FST, an effect opposite to that of standard antidepressant drugs. Doses of SalvA that produced these effects in the FST did not affect locomotor activity in an open field. Furthermore, SalvA dose dependently elevated ICSS thresholds, an effect similar to that produced by treatments that cause depressive symptoms in humans. At a dose that caused the depressive-like effects in both the FST and ICSS assays, SalvA decreased extracellular concentrations of dopamine (DA) within the nucleus accumbens (NAc), a critical component of brain reward circuitry, without affecting extracellular concentrations of serotonin (5-HT). These data provide additional support for the hypothesis that stimulation of brain kappa-opioid receptors triggers depressive-like signs in rats and raise the possibility that decreases in extracellular concentrations of DA within the NAc contribute to these effects.
- Subjects :
- Animals
Depression, Chemical
Diterpenes, Clerodane
Dopamine metabolism
Extracellular Space drug effects
Extracellular Space metabolism
Male
Microdialysis
Motor Activity drug effects
Rats
Rats, Sprague-Dawley
Serotonin metabolism
Swimming psychology
Behavior, Animal drug effects
Brain Chemistry drug effects
Diterpenes pharmacology
Psychotropic Drugs pharmacology
Receptors, Opioid, kappa agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 316
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 16223871
- Full Text :
- https://doi.org/10.1124/jpet.105.092304