Effects of meta-chlorophenylpiperazine (mCPP) on a T-maze acquisition and reversal learning task in male and female rats

Behavioral flexibility is critical for adaptive functioning and is often impaired in neuropsychiatric disorders such as obsessive–compulsive disorder (OCD). The serotonergic agent meta -chlorophenylpiperazine (mCPP), a non-selective 5-HT receptor agonist, is commonly used to model OCD-like behaviors. However, its effects on behavioral flexibility, particularly in females, remain poorly understood. This study investigated sex differences and the effects of mCPP on acquisition and reversal learning in adult Wistar rats using the T-maze task. Experiment 1 compared male and female rats during the acquisition and reversal learning phases. Experiment 2 evaluated the effects of mCPP (0.5 and 2 mg/kg) on behavioral flexibility in males and females. Behavioral measures included accuracy, omissions, and reaction time. In Experiment 1, no significant differences were observed between males and females during acquisition or reversal learning. In Experiment 2, mCPP at 2 mg/kg impaired reversal learning in males, as shown by increased omissions and reaction time. In females, the same dose disrupted both acquisition and reversal learning, with increased omissions and reaction time, and reduced accuracy. These findings indicate that mCPP disrupted cognitive performance in both sexes, with more pronounced and broader impairments in females. These results highlight the importance of including both sexes in preclinical models for behavioral flexibility and support the relevance of serotonergic modulation in vulnerability to behavioral inflexibility.