Gonadal Hormones and Aggression‐Maintaining Effect of Alcohol in Male Transgenic Transforming Growth Factor‐α Mice

We have characterized a new transgenic mouse model that offers the unique opportunity to study the biological mechanisms linking aggression to alcohol. In contrast to all other aggressive animal models, the male transgenic mice that overexpress transforming growth factor‐α (TGF‐α) maintain their highly elevated aggressive behavior following an alcohol administration. The transgenic mice also exhibit elevated plasma levels of 17β‐estradiol (E2). Animal data support the role of E2 in aggression and alcohol intake in males. Further, type 2 alcoholism is male‐limited, suggesting that gonadal hormones are important. We examined whether gonadal hormones play a role in the resistance to respond to alcohol in the resident‐intruder test of aggression among the male transgenic TGF‐α mice. As previously reported, alcohol had a biphasic effect on sham‐operated, nontransgenic controls: 0.6 g/kg increased and 2.0 g/kg inhibited their aggressiveness. Alcohol did not significantly reduce the high levels of aggression in the sham‐operated TGF‐α mice. Castration abolished the difference in aggressive behavior between the transgenic and nontransgenic male mice by reducing aggression. Alcohol did not increase aggressive behavior in these mice. Treatment with pellets releasing 0.25 mg E2 over a 60‐day period increased aggression in the castrated male TGF‐α mice and nontransgenic controls to the levels seen in intact male transgenic mice. Alcohol did not significantly alter aggressive behavior in the E2‐treated castrated mice. These findings suggest that gonadal hormones are linked to aggressive behavior and to the aggression‐altering effect of alcohol both in the transgenic and nontransgenic mice. In particular, high plasma levels of E2 may play a critical role in the failure of alcohol to alter aggressive behavior in aggressive male mice.