Resting State Functional Connectivity in a Mouse Model of Schedule Induced Repetitive Behavior

<p style="text-align: left;">Schedule-induced polydipsia (SIP), a form of schedule induced drinking, is often used as an animal model of compulsive mechanisms underlying addiction. SIP has been well studied in&nbsp;<br />monkeys and rats, but there are few studies on SIP on mice, particularly with water in C57BL/6J (B6) mice, which are the most used strains in pre-clinical research. Such information is critical to&nbsp;<br />understand SIP development in B6 mice and biomarkers of compulsive behavior. Male B6 mice were divided into SIP (n = 16) or CTR (n = 8) groups and were food restricted to ~85% of their&nbsp;<br />body weight starting week 1. At week 2, all mice were subjected to 15 60-min SIP sessions with water, in which SIP mice received sucrose pellets at 1-min FT, while CTR mice were mass-fed. A&nbsp;<br />subset of the mice (SIP n = 9, CTR n = 8) were examined though functional magnetic resonance imaging (fMRI) to detect changes in functional connectivity (FC) with the anterior insula (AI). fMRI scans occurred at the end of week 1 and after the 15 SIP sessions. Our findings showed that SIP mice could be split into repetitive (R) and non-repetitive (NR) drinkers. Compared to CTR mice, R SIP mice drank more often despite smaller drink sizes. CTR mice showed a&nbsp;<br />positive correlation between pellets eaten and water drank but not SIP mice. Significant FC changes were found between the AI, dentate gyrus (DG), lateral septum (LS), and entorhinal cortex (ENT). CTR mice displayed higher FC than SIP mice after SIP training. SIP mice&nbsp;<br />displayed no significant changes in FC. Our results suggest that under SIP, B6 mice develop repetitive but not excessive drinking. Moreover, the smaller drinking size of SIP mice reveals possible alternative coping strategies. The FC changes of CTR mice compared to SIP mice reveal structures involved in repetitive behavior development and its coping effect. &nbsp;