Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

Background: Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Methods: Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [C-11]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Results: Nicotine administration produced significant, dose-dependent reductions in [C-11]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Conclusions: Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.