Behavioral and biological markers for predicting compulsive-like drinking in schedule-induced polydipsia

Schedule-induced polydipsia (SIP), characterized by the development of persistent and excessive drinking under intermittent food-reinforcement schedules, is an animal model of compulsive behavior that can differentiate two populations: high drinkers (HD) and low drinkers (LD). The aim of the present study was to identify behavioral and biological markers to predict the vulnerability to developing compulsive-like drinking in SIP. Adult male Wistar rats were first trained in a spatial-discrimination serial reversal-learning task and in a reinforcer devaluation task to measure behavioral flexibility and habit formation, respectively. Subsequently, the rats were tested using the SIP protocol and identified as HD or LD based on their drinking rates. The performance of HD and LD rats in the two previous tasks was then analyzed. Before and after SIP exposure, blood glucose and plasma corticosterone (CORT) levels were measured. Additionally, serum electrolyte levels, including sodium, potassium, and chloride, were analyzed after SIP. HD rats showed higher behavioral inflexibility by exhibiting increased perseverative responses in the reversal-learning task and insensitivity to reinforcer devaluation during extinction under selective satiation. After SIP exposure, HD rats exhibited increased basal plasma CORT levels, indicating that this vulnerable group might have a dysregulation of the HPA axis. Although HD and LD rats had blood glucose levels within normal range, the HD group showed lower levels. The HD group did not exhibit hyponatremia (i.e., reduced serum sodium levels) when compared to LD rats after 20 daily SIP sessions. The results of the present study demonstrated that HD rats exhibit behavioral inflexibility and greater habitual-like behavior before SIP. Moreover, these results highlight the importance of measuring different behavioral and biological markers for predicting the vulnerability to developing compulsivity, and for enhancing the understanding of the pathophysiology of compulsive spectrum disorders.