Abstract
Introduction: Morphine is a potent analgesic with a high potential for addiction. Emerging evidence suggests that natural products may offer therapeutic benefits in addiction management. Therefore, this study aimed to evaluate the effects of Astragalus fasciculifolius extract on morphine-seeking behavior in a mouse model subjected to acute stress. The study also investigated how A. fasciculifolius influences morphine-induced conditioned place preference (CPP) and related biochemical changes in stressed mice.
Methods: Forty-two male NMRI mice were randomly assigned to seven groups: control, morphine, morphine + saline, morphine + stress, and A. fasciculifolius-treated groups receiving 150, 450, or 800 mg/kg doses. After completing five days of CPP behavioral assessments, the mice were anesthetized via the intraperitoneal administration of ketamine and xylazine. Then, blood samples were collected via cardiac puncture, and hippocampal tissue was isolated. Finally, malondialdehyde (MDA) levels, total antioxidant capacity (TAC), and messenger RNA expression of brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha in the hippocampus were quantified.
Results: Morphine administration significantly increased CPP scores compared to controls (P < 0.001). Acute stress further amplified morphine preference in stressed mice relative to non-stressed morphine-treated mice. Moreover, A. fasciculifolius at 800 mg/kg markedly attenuated morphine-seeking behavior in stressed mice and substantially enhanced TAC while reducing MDA levels in both hippocampus and serum (P < 0.001).
Conclusion: Our findings confirmed the exacerbating effect of stress on morphine-seeking behavior, suggesting that A. fasciculifolius may offer protective benefits by modulating oxidative stress and neuroinflammatory markers.