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.