The Effects of Hydroalcoholic Extract of Satureja khuzestanica on Naloxone-Induced Morphine Withdrawal Symptoms in Wistar Rats

Abstract
Introduction: The inflammatory system, oxidative stress, and cholinergic pathways are some important factors in long-term opioid dependence withdrawal. The adverse effects of some adjunctive medications on withdrawal symptoms treatment limit their clinical efficiency and finding compounds with inhibitory effects on opioid dependence can be helpful. The antioxidant, antinociceptive, and anti-inflammatory properties of Satureja khuzestanica extract (SKE) have been noted. Additionally, it could reduce morphine analgesic tolerance. Given that no study has assessed the effect of SKE on morphine-induced withdrawal symptoms, we have tried to investigate it in this study. Methods: Male Wistar rats were used in this study. The rats were treated with morphine for 7 days. The control group received saline, and intervention groups received SKE intragastrically by gavage (100 mg/kg, 50 mg/kg, and 25 mg/kg) 15 minutes before morphine injections. Five hours after the last injection, naloxone was used and withdrawal symptoms were assessed for one hour. SPSS software version 16.0 was used for statistical analysis, and P≤0.05 was considered statistically significant. Results: SKE diminished weight loss and jumping (P≤0.001). It decreased grooming behaviors and cramps (P≤0.01). SKE was found to decrease morphine withdrawal symptoms and 100 mg/kg was the most effective dose. Additionally, different doses of SKE were able to eliminate ptosis, diarrhea, and teeth chattering in animals; however, different doses had different effects on withdrawal symptoms. Conclusion: Naloxone significantly increased the frequency of jumping, cramps, weight loss, grooming, and induced ptosis, diarrhea, and teeth chattering. Treatment with SKE can significantly reduce morphine withdrawal symptoms. This can be done through its ability to decrease inflammation.