Efeitos da meta-clorofenilpiperazina (mCPP) na flexibilidade comportamental avaliada na tarefa de deslocamento de regras em ratos machos e fêmeas

Abstract

Behavioral flexibility, the ability to rapidly adapt behavior to changes in the environment, is a central component of cognitive functioning and is frequently impaired in neurological and psychiatric conditions. Investigating its neural bases aims to broaden its understanding and improve therapeutic interventions. The set-shifting task is widely used to assess behavioral flexibility, examining the ability to adjust behavior in response to dynamic environmental demands. Among the factors influencing this ability, serotonin plays an important role, particularly via 5-HT2C receptors. Meta-chlorophenylpiperazine (mCPP), a non-selective serotonergic agonist with high affinity for 5-HT2C receptors, has been frequently employed in research; however, its influence on set-shifting performance had not yet been explored. The present study investigated the effects of different doses of mCPP (0; 0.5; 1; 2 mg/kg) on the behavioral flexibility of adult male and female Wistar rats, aiming to characterize potential sex differences and their pharmacological modulation. As expected, mCPP impaired behavioral flexibility in both males and females, albeit with a complex and sexually dimorphic pattern of effects. In males, the main effects occurred at 0.5 mg/kg dose, which reduced accuracy and increased omissions and perseverative errors. Females showed greater sensitivity to the 2.0 mg/kg dose, with impairments characterized by increased reaction time and omissions, without reduced accuracy. Baseline sex differences were observed, suggesting greater task flexibility in males, a pattern that persisted following mCPP treatment. Taken together, the results indicate that mCPP reduces behavioral flexibility, differentially affecting performance in males and females, with implications for understanding sex differences in psychiatric conditions characterized by behavioral inflexibility.