RESUMO
OBJECTIVE: To determine if carriers of the allelic expression of the G variant of the human mu opioid receptor (OPRM1) A118G polymorphism have greater increases in striatal dopamine (DA) release after tobacco smoking. METHODS: Nineteen of 20 genotyped male tobacco smokers, after overnight abstinence, smoked denicotinized (denic) and average nicotine (nic) containing tobacco cigarettes in a PET brain imaging study using [(11)C]raclopride. RESULTS: The right striatum had more free D(2) receptors than the left striatum pre- and post-tobacco smoking. After smoking the nic cigarettes, mean decreased DA binding was observed in the left dorsal caudate (-14 6 11; t=3.77), left and right ventral putamen (-26 3-8; t=4.27; 28 2 1; t=4.25, respectively), and right caudate (17 18 1; t=3.92). The effects of A118G genotype on the binding potentials for these four regions were then analyzed. Carriers of the G allele had larger magnitudes of DA release in response to nic smoking than those homozygous for the more prevalent AA allele in the right caudate and right ventral pallidum (t=3.03; p=0.008 and t=3.91; p=0.001). A voxel by voxel whole brain SPM analysis using an independent samples t test did not reveal any other differences between genotype groups. In addition, the venous plasma cortisol levels of the volunteers from 8:30 a.m. to 12:40 p.m. were lower in the AG/GG allele carriers. Nic smoking increased plasma cortisol in both groups, but they were higher in the AA group. CONCLUSION: This preliminary study indicates a difference in both brain striatal DA release and plasma cortisol in A118G polymorphic male tobacco smokers.
