Abstract
104
Objectives Exposure to nicotine and cigarette smoke have been known to cause 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 determined with positron emission tomography (PET) and the aromatase PET tracer, [11C]vorozole(>4.4 mCi/nmole, 1.9-6.3 mCi) in six female baboons before and after intravenous administration of nicotine at 0.015 and 0.03 mg/Kg. Blood samples were collected for determination of [11C]vorozole input function and concentration of nicotine and cotinine over a dynamic 90 min PET scan. Time-activity curves and the arterial input function were used to calculate K1 (the plasma to brain transfer term) and VT (the total volume of distribution).
Results Nicotine administration produced significant and dose dependent reductions in[11C]vorozole binding (VT)with the largest reductions in the amygdala (-39%) and preoptic area (-29%). There was no change in K1. 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 revealing another mechanism by which nicotine and cigrette smoking could exert their effects on behavior and physiology.
Research Support NIAAA, NIDA and DOE-OBER (infrastructure)