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Introduction: Nitric oxide (NO) is a neuronal messenger molecule in the central nervous system, which is generated from L-arginine by nitric oxide synthase (NOS) and involves in many important opioid-induced effects. Our previous studies revealed that Cuminum cyminum interestingly reduces morphine sensitization, tolerance and dependency in male mice. Therefore, in the present study, the effect of intraperitoneal (ip) administration of different doses of cumin fruit essential oil (FEO) on the acquisition of morphine-induced conditioned place preference (CPP) in L-arginine treated mice was investigated. Methods: In this study, the CPP paradigm was done on 231 adult male albino Wistar mice and conditioning scores and locomotor activity were recorded by the Ethovision software. Results: The results showed that solely administration of different doses of cumin FEO (0.01, 0.1, 0.5, 1 and 2% ip) or L-arginine (50, 100 and 200 mg/kg ip) during CPP protocol could not induce CPP. Nonetheless, morphineinduced CPP was significantly decreased by two higher doses of cumin FEO (1% and 2% P<0.05), while it was increased by L-arginine (100 and 200 mg/kg) when they were injected before morphine (5 mg/kg) during the acquisition period (P<0.001). Additionally, cumin FEO (0.01-2%) could interestingly attenuate the increasing effect of L-arginine (200 mg/kg) on morphine-induced CPP in a dose-dependent manner. Conclusion: In conclusion, it could be suggested that some components of cumin FEO attenuate the excessive effect of L-arginine on morphine-induced CPP through inhibitory mechanisms on NO pathway. It seems that cumin FEO possibly acts as a NOS inhibitor.

Keywords: Cuminum cyminum, Nitric oxide, Morphine, L-Arginine, Conditioned place preference, Acquisition, Mice

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