Melatonin attenuates morphine-induced conditioned place preference in Wistar rats

Abstract

Purpose: Morphine is the predominantly used drug for postoperative and cancer pain management. However, the abuse potential of morphine is the primary disadvantage of using opioids in pain management. Melatonin is a neurohormone synthesized in the pineal gland and is involved in circadian rhythms in mammals, as well as other physiological functions. Melatonin provenly attenuates alcohol-seeking and relapse behaviors in rats. Therefore, we aimed to investigate the involvement of the melatonergic system in attenuating morphine dependence. Materials and methods: Male Wistar rats were divided into three groups: control, morphine, and morphine + melatonin. Animals were habituated for 3 days, and the initial preference was evaluated. Following the initial preference, the control group received the vehicle and was placed for a 45-min session in the assigned chamber every day, alternating between the two chambers, for 8 days. The morphine group received a morphine injection (5 mg/kg, IP) and was placed for a 45-min session in the white chamber, for a total of four sessions. The morphine + melatonin group received the morphine injection (5 mg/kg, IP) for a total of four sessions over an 8-day period. In the posttest session, the control and morphine groups received a vehicle injection 30 min before placement in the conditioned place preference (CPP). The morphine + melatonin group received a single injection of melatonin (50 mg/kg, IP) 30 min before the preference test. Results: Statistical analysis revealed that repeated administration of morphine for four sessions produced a significant increase in the CPP score in the morphine group compared to the control group. However, a single melatonin injection administered 30 min before the posttest attenuated morphine-seeking behavior and reduced morphine-induced place preference. Conclusion: These findings provide novel evidence for the role of the melatonergic system as a potential target in modulating morphine-seeking behavior.