Kisspeptin-13 attenuates the rewarding but not the reinstatement effects of methamphetamine in the conditioned place preference test in rats

Introduction: Methamphetamine (MA) addiction is a major global public health concern, yet there is currently no approved medication that effectively treats this addiction.Kisspeptin is a neuropeptide that has a role in the reproductive system, metabolism and energy balance, and metastasis suppression in different types of cancers.The kisspeptin receptors, GPR54 are widely distributed in the brain's memory-related structures.Previous studies have revealed that the opioid system contributes to the addictive effects of MA.Additionally, preclinical studies have shown that a derivative of kisspeptin possesses anti-opioid properties.This study aimed to clarify the role of kisspeptin-13 (KP-13) on reward and reinstatement-related memory associated with MA in the conditioned place preference test.Methods: We evaluated pre-treatment with intracerebroventricular KP-13 for 3 consecutive days (2.5 l/nostril, once a day) in a conditioned place preference test induced by MA.MA was administered intraperitoneally at a dose ranging from 1 to 7 mg/kg, once daily, beginning at 1 mg/kg on day one and increasing by 1 mg/kg per day up to the day 7. Results: We found that KP-13 suppresses the reward behavior in MA-treated rats, while it has no significant effect on reinstatement behavior after one week of MA cessation, which could be attributed to the ineffective dose of KP-13. Conclusion:The findings indicate that KP-13 alters the rewarding and motivating effects of MA.Further research involving both multiple and single administrations of KP-13 before the reinstatement test is necessary to throw light on its impact on withdrawal-related reinstatement.