title: Antidepressive effects of the κ-opioid receptor agonist salvinorin A in a rat model of anhedonia.
abstract: Salvinorin A (SalvA), the hallucinogenic derivative of the plant Salvia divinorum, is a selective κ-opioid receptor agonist that may also have antidepressant properties. Chronic mild stress (CMS) was applied to male and female Long-Evans rats to model anhedonia common in depression. The progressive loss in preference for a sucrose solution over plain water, a measure of anhedonia, and locomotor activity were monitored for 7 weeks. Because antidepressant medications often modify reproductive functions, endocrine glands and hormone-sensitive tissues were assessed at necropsy after the conclusion of the behavioral protocol. Three weeks of CMS exposure led to a decrease in sucrose preference. CMS was continued for 3 additional weeks and animals were randomly assigned to treatment with 1 mg SalvA/kg body weight or to a vehicle control group. The results indicate that SalvA reversed anhedonia whereas control animals continued to show a suppressed preference for the sucrose solution. In addition, no change in sucrose preference was observed in nonstressed rats that were exposed to the same dosage of SalvA. The results indicate that SalvA is an effective antidepressant agent when administered chronically to rats showing symptoms of depression similar to those observed in humans.
authors.affiliation: Department of Behavioral Neuroscience, University of Missouri, St Louis, Missouri 63121, USA. MTHarden@umsl.edu
authors.forename: Mitchell T
authors.initials: MT
authors.lastname: Harden
authors.forename: Staci E
authors.initials: SE
authors.lastname: Smith
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Niehoff
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCurdy
authors.forename: George T
authors.initials: GT
authors.lastname: Taylor
mesh_terms: D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D027544:Salvia / Q000737:chemistry; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D045785:Diterpenes, Clerodane; D017473:Receptors, Opioid, kappa; D013395:Sucrose; C090499:salvinorin A