Background: 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 and has a role in the reproductive system, metabolism and energy balance and suppression of metastasis in different types of cancer. 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 condition place preference test.
Methods: We evaluated pre-treatment with intracerebroventricular KP-13 for 3 consecutive days (1.5 µg/µl, ICV, once a day) in a condition place preference test induced by MA. MA was administered intraperitoneally at a dose of 1-7 mg/kg twice daily, beginning with 1 mg/kg on day one and increasing by 1 mg/kg per day for seven days.
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 non-effective dose of KP-13. The anti-reward effect of KP-13 is, however, believed to be a result of its ability to improve memory impairment caused by MA, rather than its anti-opioid properties.
Conclusions: 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.