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Modulating morphine-induced conditioned place preference: The role of diclofenac sodium

Year: 2025

Type: article

Abstract: Morphine is known to induce strong reward-related behaviors, contributing to its high addiction potential. Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac sodium, have been suggested to modulate neuroinflammatory pathways involved in addiction. This study aimed to evaluate the effect of diclofenac sodium on morphine-induced conditioned place preference (CPP) in rats and investigate its underlying anti-inflammatory and antioxidant mechanisms. Female rats were subjected to a morphine-induced conditioned place preference (CPP) protocol. Diclofenac sodium (25 mg/kg) was administered 30 minutes prior to morphine conditioning sessions via injection. Post-conditioning, brain tissue samples were analyzed to measure the mRNA expression levels of cyclooxygenase enzymes ( Cox1 , Cox2 ), nuclear factor kappa B ( Nf-κB ), interleukin-6 ( Il-6 ), and interleukin-1β ( Il-1β ). Oxidative stress in plasma samples was assessed through catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) enzyme activity. Morphine significantly induced CPP, indicating a strong reward effect. Diclofenac sodium administration markedly attenuated this morphine-induced seeking behavior. This behavioral effect was accompanied by a significant reduction in the expression levels of Cox1 , Cox2 , Nf-κB , and IL-6, and a significant increase in Il-1β mRNA levels compared to the morphine group. Additionally, diclofenac sodium significantly reduced oxidative stress, as indicated by decreased SOD activity when combined with morphine compared to the morphine group. In conclusion, Diclofenac sodium effectively attenuates morphine-induced reward behavior in the CPP model, potentially through modulation of inflammatory and oxidative stress pathways. These findings support the therapeutic potential of diclofenac sodium in managing opioid-seeking behaviors and provide insights into its anti-inflammatory and antioxidant mechanisms of action. • Diclofenac sodium effectively attenuates morphine-induced reward behavior in the CPP model. • This is potentially through modulation of inflammatory and oxidative stress pathways. • These findings support the therapeutic potential of diclofenac sodium in managing opioid-seeking behaviors and provide insights into its anti-inflammatory and antioxidant mechanisms of action.

Source: Toxicology Reports

DOI: 10.1016/j.toxrep.2025.102174