Spatial extent of ventral striatal dopamine response to cigarette smoking shows gender difference as measured by lp-ntPET analysis

Objectives Clinical findings show that women are more reinforced than men by the non-nicotine aspects of smoking, whereas men are more reinforced by the nicotine per se in cigarettes [1]. Our goal is to test whether smoking induces a greater spatial extent of dopamine (DA) response to cigarette smoking in the ventral striatum (VS) in male vs. female smokers using voxel-wise lp-ntPET analysis [2,3]. The lpntPET model is designed to detect transient DA release at the voxel level.

Methods 12 healthy human smokers (6 M, 6 F) received either one or two bolus-plus-constant-infusion (B/I) [11C]raclopride scans that included smoking one or two cigarettes while inside the HRRT PET scanner. Smoking began 35 or 45 minutes after the initial tracer bolus. Data were collected for 90 min and subject head motion was recorded using an optical tracking system. Dynamic data were reconstructed iteratively with MOLAR, including all standard corrections. Significance Masks were created by the F-test comparing the fit of each voxel-wise TAC in a striatal mask with lp-ntPET to its corresponding fit with the standard reference model MRTM, which implicitly considers DA to be time-invariant. Probability of Activation Maps were generated by summing the Significance Masks and dividing by number of M or F, separately. Statistical significance of the difference in the mean number of VS voxels activated by smoking between men and women was assessed with a permutation test.

Results The Probability of Activation Maps showed that male smokers were more likely to activate (experience DA release in) the right VS than female smokers (Fig. 1A). The mean number of voxels activated in the right VS was 22.33±7.71 for men and 4.58±1.62 for women. The difference between means in the male and female groups was 17.75±7.88. The permutation test showed the p-value for this difference in extent of activation to be 0.02 (2-tailed) (Fig. 1B).

Conclusions These data suggest that men have greater spatial extent of DA response to cigarette smoking in the right VS than women.

Research Support R21DA032791