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 μl/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.