Injections of the radiotracer alone (baseline studies, n = 8) resulted in a highly heterogeneous distribution of radioactivity; with the highest levels found in the amygdala and preoptic area (). Pretreatment with either a high (.03 mg/kg, n = 4) or a low (.015 mg/kg, n = 4) dose of nicotine administered IV 5 min before radiotracer injection resulted in a remarkable reduction of tracer uptake in the brain ().
Figure 1 Effect of nicotine pretreatment on brain aromatase Top: (A) baboon brain magnetic resonance imaging (MRI), coronal section at the level of amygdala. (B) Representative baseline positron emission tomography (PET) image coregistered with MRI. (C) The PET (more ...)
Results of the analysis of the time-activity curves in brain regions and plasma by the graphical approach (GA, 16) were compared with the results of applying the one- and two-compartment models (1C and 2C, respectively). The correlation coefficient for GA and 2C was R = .92 (fit: GA=−.042 + 1.02 × 2C), and the correlation and fit for GA and 1C was R = .702 (GA = .223 + 1.22 × 1C). Therefore, the 2-compartment model agrees well with the graphical analysis that is model independent, and the 1-compartment model underestimates the GA distribution volume. Consequently, the kinetic parameters derived from the 2C model were used in the statistical analysis of the nicotine effects.
Analysis of variance of the VT revealed highly significant effects of region [F
(5) = 4.23, p
< .002] and nicotine dose [F
(2) = 6.6, p
< .0025] and a nonsignificant region × dose interaction term (p
= .2). There were no effects on K1
, the plasma-to-brain transfer term (data not shown). Regional, paired t
statistics were also used for comparing VT before and after nicotine treatment in the same animal and day. The results of this analysis () show that .03 mg/kg nicotine produced a significant reduction in VT in the amygdala (39%, p
< .015), preoptic area (29%, p
< .05), and striatum (18%, p
< .02), with nonsignificant trends in the same direction in cerebellum (21%, p
= .065), whole brain (20%, p
= .054), and cortical white matter (10%, p
= .075). In comparison, injection of a pharmacological dose of unlabeled vorozole (13
) reduced VT by 57%, 41%, and 21% in the amygdala, preoptic area, and cortical white matter, respectively (data not shown).
Two minutes after injection of nicotine (3 min before radiotracer injection), plasma levels ranged from 15.6 ng/mL (low dose) to 65 ng/mL (high dose, ). Nicotine levels declined exponentially with time (). In parallel, plasma cotinine levels rose from 24–37.8 ng/mL at 2 min to 35–63 ng/mL at 90 min after nicotine injection.
Figure 2 Dose-related plasma levels of nicotine in female baboons. The circles (blue line) depictmeannicotine plasma levels in four animals injected with .03 mg/kg nicotine IV. The triangles (purple line) depict nicotine levels in two animals injected with .015 (more ...)