Antidepressive effects of the κ-opioid receptor agonist salvinorin A in a rat model of anhedonia.

Summary

Salvinorin A (SalvA) reversed anhedonia in rats subjected to chronic mild stress, while control animals maintained a reduced preference for sucrose. After three weeks of stress, rats treated with 1 mg SalvA/kg body weight showed increased sucrose preference compared to the vehicle group. In contrast, nonstressed rats given the same dosage did not exhibit any change in sucrose preference. These findings suggest that SalvA may be an effective antidepressant for conditions resembling human depression.

Study at a glance

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.