Compulsive behavior in the 5-HT2C receptor knockout mouse

• Published in: Physiology & behavior 2003-04, Vol.78 (4-5), p.641-649
• Main Authors: CHOU-GREEN, Jennifer M, HOLSCHER, Todd D, DALLMAN, Mary F, AKANA, Susan F
• Format: Article
• Language: English
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Compulsive Behavior - genetics; Compulsive Behavior - psychology; Eating - genetics; Eating - physiology; Exploratory Behavior - physiology; Fundamental and applied biological sciences. Psychology; Genotype; Habituation, Psychophysiologic - genetics; Habituation, Psychophysiologic - physiology; Hyperphagia - genetics; Hyperphagia - psychology; Mastication - genetics; Mastication - physiology; Mice; Mice, Knockout; Neurotransmission and behavior; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptor, Serotonin, 5-HT2C - genetics; Receptor, Serotonin, 5-HT2C - physiology
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/s0031-9384(03)00047-7

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.