Estrogen deficient male mice develop compulsive behavior

Biol Psychiatry. 2007 Feb 1;61(3):359-66. doi: 10.1016/j.biopsych.2006.01.012. Epub 2006 Mar 29.


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 17beta-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 17beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatase / genetics
  • Aromatase / physiology
  • Blotting, Western
  • Brain / enzymology
  • Catechol O-Methyltransferase / genetics
  • Catechol O-Methyltransferase / metabolism
  • Compulsive Behavior / genetics
  • Compulsive Behavior / physiopathology*
  • Compulsive Behavior / psychology*
  • Estradiol / pharmacology
  • Estrogens / deficiency*
  • Estrogens / pharmacology
  • Female
  • Grooming / physiology
  • Liver / enzymology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology


  • Estrogens
  • Estradiol
  • Aromatase
  • Catechol O-Methyltransferase