Lower dopamine D2/3 receptor availability is associated with worse verbal learning and memory in people who smoke cigarettes

March 20, 2023

Authors: Yasmin Zakiniaeiz, Ralitza Gueorguieva, Mac Kenzie R Peltier, Walter Roberts, Terril L Verplaetse, Catherine Burke, Evan D Morris, Sherry A McKee, Kelly P Cosgrove

Journal: Nicotine & Tobacco Research

DOI: 10.1093/ntr/ntac215

Year Published: 2022


Tobacco smoking is a major public health burden. The mesocortical dopamine system-including the dorsolateral prefrontal cortex (dlPFC)-plays an important role in cognitive function. Dysregulated dopamine signaling in dlPFC is associated with cognitive deficits such as impairments in attention, learning, working memory, and inhibitory control. We recently showed that dlPFC dopamine D2/3-type receptor (D2R) availability was significantly lower in people who smoke than healthy-controls and that dlPFC amphetamine-induced dopamine release was lower in females who smoke relative to males who smoke and female healthy-controls. However, we did not examine whether the smoking-related dopamine deficits were related to cognitive deficits. The goal of this study was to relate dopamine metrics to cognitive performance in people who smoke and healthy-controls.


Twenty-four (12 female) people who smoke cigarettes and 25 sex- and age-matched healthy-controls participated in two same-day [ 11C]FLB457 positron emission tomography (PET) scans before and after amphetamine administration. Two outcome measures were calculated – D2R availability (non-displaceable binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND). Cognition (verbal learning and memory) was assessed with a computerized test from the CogState battery (International Shopping List).


People who smoke had significantly worse immediate (p=0.04) and delayed (p=0.03) recall than healthy-controls. Multiple linear regression revealed that for people who smoke only, lower D2R availability was associated with worse immediate (p=0.04) delayed recall (p<0.001). %ΔBPND was not significantly related to task performance.


This study demonstrated that lower dlPFC D2R availability in people who smoke is associated with disruptions in cognitive function that may underlie difficulty with resisting smoking.


This is the first study to directly relate dopamine metrics in the prefrontal cortex to cognitive function in people who smoke cigarettes compared to healthy-controls. The current work included a well-characterized subject sample with regards to demographic and smoking variables, as well as a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature by relating dopamine metrics to cognition in people who smoke, providing a better understanding of brain-behavior relationships.

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