Pharmacological analysis of the role of kisspeptin-10 in reinforcing mechanisms

Introduction: Behavioral and substance addictions are driven by shared neurobiological mechanisms, often involving the reward system. Kisspeptin-10, a neuropeptide primarily linked to reproductive functions, has emerged as a potential modulator of reward-related behaviors and decision-making. This study explores the effects of kisspeptin-10 on impulsivity, compulsivity, and reinforcement mechanisms. Materials and Methods: Male Wistar rats were used to assess the effects of kisspeptin-10 on behavior. A conditioned place preference (CPP) test evaluated reinforcement effects at doses of 0.1 mg/kg, 0.5 mg/kg, and 1 mg/kg. A modified Iowa Gambling Task analyzed decision-making and impulsivity under variable reinforcement schedules. The marble-burying test was employed to assess compulsive behaviors. Statistical analysis included one-way ANOVA and Tukey's post-hoc test. Results and Discussion: Kisspeptin-10 at 1 mg/kg induced a significant CPP response, suggesting reinforcing properties. In the gambling task, kisspeptin-10 enhanced impulsive choices by increasing preference for riskier reinforcement schedules, contrasting with the stabilizing effects of paroxetine. In the marble-burying test, kisspeptin-10 increased compulsive behavior compared to paroxetine, underscoring its modulatory role in compulsivity. These effects likely reflect kisspeptin-10’s interaction with dopaminergic and serotonergic systems, extending its influence beyond reproductive functions. Conclusion: Kisspeptin-10 dose 1 mg/kg significantly modulates impulsive and compulsive behaviors, as well as reinforcing mechanisms, highlighting its potential as a therapeutic target for conditions characterized by dysregulated decision-making and compulsivity.