Activation of the orbitofrontal and anterior cingulate cortices during the expression of a naturalistic compulsive-like behavior in the rabbit

Abstract

We propose that maternal nest building in the female laboratory rabbit is a useful model for compulsions in obsessive-compulsive disorder (OCD). This repetitive behavior comprises collecting straw, depositing it into the nest box, and then returning to collect more straw. We reasoned that if “straw carrying” behavior is homologous to compulsive behavior, then it should be associated with activation of prefrontal regions associated with OCD, namely, the orbitofrontal and anterior cingulate cortices (OFC and ACC, respectively). In the present study, we quantified c-FOS immunoreactivity in the ACC, OFC, premotor (PM), infralimbic (IL), prelimbic (PL), and piriform (PI) cortices of: (1) pregnant female rabbits that were given straw (PREG+STRAW); (2) pregnant rabbits that were not given straw (PREG); (3) estrous rabbits that were given straw (ESTROUS+STRAW); (4) estrous rabbits that were not given straw (ESTROUS). After 1h, all females were sacrificed and processed for brain c-FOS immunoreactivity. We found that pregnant rabbits showed lower latencies to interact with the straw than estrous rabbits, and that pregnant rabbits displayed straw carrying, while estrous rabbits did not. c-FOS expression was increased in the OFC, ACC, and PI in the PREG+STRAW compared to all other groups. By contrast, c-FOS expression in all other regions was greater in PREG+STRAW compared to PREG, but not different from ESTROUS+STRAW. These results point to an important role for the OFC, ACC, and PI in initiating repetitive straw-carrying behavior, and further support the proposal that this behavior can serve as a model for compulsions in OCD.