Compulsive behavior in the 5-HT2C receptor knockout mouse

The efficacy of serotonergic pharmacotherapy indicates that serotonin (5-HT) plays a role in the treatment, if not the etiology, of obsessive–compulsive disorder (OCD). While some clinical evidence implicates 5-HT 2C receptors in this disorder, a definitive function has yet to be validated. We hypothesized that 5-HT 2C receptor knockout (KO) mice may display compulsive-like behavior. This paper describes characterization of several distinct, highly organized behaviors in mice lacking functional 5-HT 2C receptors, which supports a compulsive-like syndrome. Compulsive-like behavior was assessed in male 5-HT 2C receptor KO and wildtype (WT) mice. Chewing of non-nutritive clay, chewing patterns on plastic-mesh screens, and the frequency of head dipping were measured. 5-HT 2C receptor KO mice chewed more clay, produced a distinct pattern of “neat” chewing of plastic screens and exhibited reduced habituation of head dipping activity compared to WT mice. We conclude that the 5-HT 2C receptor null mutant mouse provides a promising model of compulsive behavior and a means to further explore the role of 5-HT in OCD.