Sex differences in amphetamine-induced dopamine release in the dorsolateral prefrontal cortex of tobacco smokers.
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ABSTRACT: 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 D2/3-type receptor (D2R) 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 [11C]FLB457 positron emission tomography (PET) scans before and 3-hours after amphetamine administration (0.4-0.5?mg/kg, PO). D2R availability (non-displaceable binding potential; BPND) was measured pre- and post-amphetamine. The percent fractional change in BPND (%?BPND) between pre- and post-amphetamine, an index of DA release, was compared between male and female smokers and nonsmokers. Smokers showed significantly lower dlPFC D2R availability (BPND?=?0.77?±?0.05) than nonsmokers (BPND?=?0.92?±?0.04), p?=?0.016, driven by males. Female smokers showed significantly less amphetamine-induced DA release in dlPFC (%?BPND?=?1.9?±?3.0%) than male smokers (%?BPND?=?14.0?±?4.3%), p?ND?=?9.3?±?3.3%), p?2R availability than nonsmokers and that female vs. male smokers have a blunted amphetamine-induced DA release. These findings demonstrate that tobacco smoking differentially affects the mesocortical DA system in men vs. women, suggesting a potential target for gender-specific treatments.
SUBMITTER: Zakiniaeiz Y
PROVIDER: S-EPMC6897943 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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