Role of estradiol in alcohol intake and alcohol-related behaviors

Objective: Gonadal hormone estrogen affects many alcohol related behaviors, including aggression and depression. Alcohol, on the other hand, alters circulating gonadal hormone levels. The present study investigated whether estrogen influences voluntary alcohol intake in male and female mice. Method: Alcohol-related behaviors of outbred CD-1 mice, which were implanted with pellets that released over a 60-day period either 0.1 or 0.25 mg 17β- estradiol (E2) or 1.5 or 5 mg anti-estrogen tamoxifen, were studied. Results: Male mice treated with E2 exhibited significantly higher levels of voluntary alcohol consumption than the tamoxifen-treated males. In contrast, tamoxifen- treated ovariectomized female mice consumed significantly more alcohol than the E2-treated ovariectomized females. Immobility in the swim test model of depressive behavior was not altered by treatment with E2 or tamoxifen. However, E2 reversed the gonadectomy induced lengthening in immobility in the swim test both in males and females. E2 increased aggression in the resident- intruder test in males, but failed to affect females. Tamoxifen or gonadectomy did not affect aggressive behavior in either sex. Conclusions: These findings suggest that E2 stimulates alcohol consumption and aggression in male mice, but it is not required to maintain baseline levels of these behaviors. Thus, elevated serum levels of E2 may link alcohol abuse and aggression in males. In female mice, low E2 levels are associated with increased immobility in the swim test and possibly with increased alcohol intake.