Purpurin exerted antidepressant-like effects on behavior and stress axis reactivity: evidence of serotonergic engagement.

Rationale And Objectives: Major depression represents a significant public health problem worldwide, and effective regimen is lacking. The present study investigated the antidepressant-like effects of purpurin, a natural anthraquinone compound from Rubia tinctorum L., and explored the underlying mechanism(s).

Methods: Forced swim test (FST) and tail suspension test (TST) were used to assess antidepressant-like effects of purpurin in mice. Effects of purpurin on neuroendocrine responsivity were evaluated at the level of corticosterone and ACTH following acute restraint stress and intracerebroventricular injection of corticotrophin-releasing-factor (CRF). Serotonergic mechanisms underlying purpurin antidepressant effect were explored using biochemical, neurochemical, and pharmacological paradigms.

Results: Chronic purpurin treatment exerted in mice dose-dependently antidepressant-like effects on behavior and stress axis reactivity (n = 9-11 per group). The purpurin-triggered antidepressant-like effects are serotonergically dependent, since purpurin-treated mice showed escalated levels of brain serotonin and suppressed monoamine oxidase (MAO) activity (n = 8-11 per group). Consistently, chemical depletion of brain serotonin by p-chlorophenylalanine (PCPA) abolished the antidepressant-like effects of purpurin on behavior and stress axis responsivity (n = 9-10 per group). Moreover, the antidepressant effect by purpurin was preferentially counteracted by 1A-selective 5-HT receptor antagonist WAY-100635, but potentiated by 1A-selective agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine (n = 9-11 per group), suggesting a crucial role for 5-HT related serotonergic system in mediating such purpurin antidepressant effect.

Conclusion: We have revealed the antidepressant-like effects of purpurin on both behavior and stress axis reactivity in mice, with serotonergic system that preferentially couples with 5-HT receptors being critically engaged.