Sex Differences in Midbrain Dopamine D2-Type Receptor Availability and Association with Nicotine Dependence

Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BP ND ) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BP ND and in relationships between midbrain BP ND, nicotine dependence and striatal dopamine D2-type receptor BP ND . Positron emission tomography was used with [ 18 F]fallypride to measure BP ND in a midbrain region, encompassing the substantia nigra and ventral tegmental area, in 18 daily smokers (7 women, 11 men) and 19 nonsmokers (10 women, 9 men). A significant sex-by-group interaction reflected greater midbrain BP ND in female but not male smokers than in corresponding nonsmokers (F 1, 32 =5.089, p =0.03). Midbrain BP ND was positively correlated with BP ND in the caudate nucleus and putamen in nonsmokers and female smokers but not in male smokers and with nicotine dependence in female but not in male smokers. Striatal BP ND was correlated negatively with nicotine dependence and smoking exposure. These findings extend observations on dopamine D2-type receptors in smokers and suggest a sex difference in how midbrain dopamine D2-type autoreceptors influence nicotine dependence.