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Compulsive behavior in the 5-HT2C receptor knockout mouse
Jennifer M Chou-Green1, Todd D Holscher, Mary F Dallman
1Department of Physiology, University of California-San Francisco, 513 Parnassus Avenue, Box 0444, San Francisco, CA 94143, USA.
Abstract:
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.
Insights
Mice lacking serotonin 5-HT(2C) receptors exhibit compulsive-like behaviors, including increased clay chewing and altered screen chewing patterns. This finding supports the role of serotonin in obsessive-compulsive disorder (OCD) and validates a new animal model.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Serotonergic pharmacotherapy is effective for obsessive-compulsive disorder (OCD), suggesting serotonin's (5-HT) involvement in its etiology or treatment.
- Clinical evidence implicates 5-HT(2C) receptors in OCD, but their precise function remains unconfirmed.
Purpose of the Study:
- To investigate the potential role of 5-HT(2C) receptors in compulsive behavior.
- To characterize behaviors in mice lacking functional 5-HT(2C) receptors (KO mice) to determine if they exhibit a compulsive-like syndrome.
Main Methods:
- Assessment of compulsive-like behavior in male 5-HT(2C) receptor knockout (KO) and wildtype (WT) mice.
- Measurement of non-nutritive clay chewing, plastic-mesh screen chewing patterns, and head dipping frequency.
Main Results:
- 5-HT(2C) receptor KO mice demonstrated significantly increased chewing of non-nutritive clay compared to WT mice.
- KO mice exhibited a distinct "neat" chewing pattern on plastic screens.
- Reduced habituation of head dipping activity was observed in KO mice relative to WT controls.
Conclusions:
- The 5-HT(2C) receptor null mutant mouse presents a promising animal model for studying compulsive behavior.
- This model facilitates further exploration into the role of serotonin (5-HT) in the pathophysiology of OCD.