Sex differences in amphetamine-induced dopamine release in the dorsolateral prefrontal cortex of tobacco smokers

Sex differences exist in the neurochemical mechanisms underlying tobacco smoking and smoking-related behaviors. Men tend to smoke for the reinforcing effects of nicotine, whereas women tend to smoke for stress and mood regulation, and have a harder time maintaining long-term abstinence. The mesolimbic dopamine (DA) system drives the reinforcing effects of tobacco smoking, whereas the mesocortical DA system-including the dorsolateral prefrontal cortex (dlPFC)-is critical for stress-related cognitive functioning and inhibitory control. This study is the first to investigate dlPFC D -type receptor (D R) availability and amphetamine-induced cortical DA release in smokers and nonsmokers. Forty-nine subjects (24 tobacco smokers (12 females) and 25 sex- and age-matched nonsmokers) participated in two same-day [ C]FLB457 positron emission tomography (PET) scans before and 3-hours after amphetamine administration (0.4-0.5 mg/kg, PO). D R availability (non-displaceable binding potential; BP ) was measured pre- and post-amphetamine. The percent fractional change in BP (%ΔBP ) between pre- and post-amphetamine, an index of DA release, was compared between male and female smokers and nonsmokers. Smokers showed significantly lower dlPFC D R availability (BP = 0.77 ± 0.05) than nonsmokers (BP = 0.92 ± 0.04), p = 0.016, driven by males. Female smokers showed significantly less amphetamine-induced DA release in dlPFC (%ΔBP = 1.9 ± 3.0%) than male smokers (%ΔBP = 14.0 ± 4.3%), p