Estrogen Deficient Male Mice Develop Compulsive Behavior

• Published in: Biological psychiatry (1969) 2007-02, Vol.61 (3), p.359-366
• Main Authors: Hill, Rachel A, McInnes, Kerry J, Gong, Emily C.H, Jones, Margaret E.E, Simpson, Evan R, Boon, Wah Chin
• Format: Article
• Language: English
• Subjects: Animals; Aromatase; Aromatase - genetics; Aromatase - physiology; Blotting, Western; Brain - enzymology; Catechol O-Methyltransferase - genetics; Catechol O-Methyltransferase - metabolism; catechol- O-methyltransferase; Compulsive Behavior - genetics; Compulsive Behavior - physiopathology; Compulsive Behavior - psychology; Estradiol - pharmacology; estrogen; Estrogens - deficiency; Estrogens - pharmacology; Female; Grooming - physiology; knockout mouse; Liver - enzymology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity - physiology; obsessive-compulsive; Psychiatry
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.01.012

Background Aromatase converts androgen to estrogen. Thus, the aromatase knockout (ArKO) mouse is estrogen deficient. We investigated the compulsive behaviors of these animals and the protein levels of catechol–O–methyltransferase (COMT) in frontal cortex, hypothalamus and liver. Methods Grooming was analyzed during the 20-min period immediately following a water-mist spray. Running wheel activity over two consecutive nights and barbering were analyzed. COMT protein levels were measured by Western analysis. Results Six-month old male but not female ArKO mice develop compulsive behaviors such as excessive barbering, grooming and wheel-running. Excessive activities were reversed by 3 weeks of 17β-estradiol replacement. Interestingly, the presentation of compulsive behaviors is accompanied by concomitant decreases ( p < .05) in hypothalamic COMT protein levels in male ArKO mice. These values returned to normal upon 17β-estradiol treatment. In contrast, hepatic and frontal cortex COMT levels were not affected by the estrogen status, indicating region- and tissue-specific regulation of COMT levels by estrogen. No differences in COMT levels were detectable between female animals of both genotypes. Conclusions This study describes the novel observation of a possible link between estrogen, COMT and development of compulsive behaviors in male animals which may have therapeutic implications in obsessive compulsive disorder (OCD) patients.