Heightened aggressive behavior in mice deficient in aldo-keto reductase 1a (Akr1a).

Aldehyde reductase (Akr1a) is involved in the synthesis of ascorbic acid (AsA) which may play a role in social behavior. In the current study, we performed analyses on Akr1a-deficient (Akr1a-/-) mice that synthesize about 10% as much AsA as wild-type mice from the viewpoint of intermale aggression. The use of the resident-intruder test revealed that the Akr1a-/- mice exhibited more aggressive phenotypes than wild-type control mice. Unexpectedly, however, the oral administration of additional AsA failed to reduce the aggressive behavior of Akr1a-/- mice, suggesting that the heightened aggression was independent of AsA biosynthesis. The findings also show that the plasma levels of corticosterone, but not serotonin and testosterone, were increased in the absence of Akr1a in mice, suggesting that the mice were highly stressed. These results suggest that Akr1a might be involved in the metabolism of steroids and other carbonyl-containing compounds and, hence, the absence of Akr1a results in heightened aggression via a malfunction in a metabolic pathway.