Abstract
BACKGROUND: Astaxanthin (AST) is a potent carotenoid with antioxidant properties that has garnered attention for its potential neuropharmacological effects. PURPOSE: This study investigates the anxiolytic and antidepressant activities of AST in a rat model to elucidate its therapeutic potential for mood disorders. MATERIAL AND METHODS: Fifty-four male rats were divided into nine groups receiving normal saline, astaxanthin (AST, 5, 10, and 15 mg/kg), diazepam (DZP, 0.5 mg/kg), fluoxetine (FXT, 5 mg/kg), or combinations of AST (10 mg/kg) with receptor antagonists flumazenil (FLU, GABA-A antagonist), atropine (ATR, muscarinic antagonist), and naloxone (NAL, opioid antagonist) for 14 consecutive days. At the end of the study, behavioral assessments were conducted, including the open field, light-dark box, elevated plus maze, tail suspension, and forced swimming tests. Biochemical analyses were performed to evaluate serum catalase (CAT), glutathione (GSH), nitrite, and matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. RESULTS AND DISCUSSION: Astaxanthin, particularly at 10 mg/kg, significantly reduced anxiety- and depressive-like behaviors, comparable to DZP and FXT in four-week-old male Wistar rats. Pretreatment with FLU, ATR, or NAL partially reversed these effects, suggesting involvement of GABAergic, cholinergic, and opioid pathways. Furthermore, AST enhanced antioxidant defenses, evidenced by increased serum CAT and GSH levels and reduced nitrite concentrations. Gelatin zymography revealed that AST increased MMP-2 activity while slightly decreasing MMP-9 activity, a partial reversal by the aforementioned antagonists. CONCLUSION: The results suggest that AST could produce anxiolytic and antidepressant effects. Such effects are likely mediated through GABAergic, cholinergic, and opioid systems, as well as antioxidant and anti-inflammatory mechanisms. Future studies should focus on well-controlled clinical trials to evaluate the preclinical results.