Lower Dorsal Putamen D2/3 Receptor Availability and Amphetamine-Induced Dopamine Release are Related to Poorer Cognitive Function in Recently Abstinent People Who Smoke and Healthy Controls

Abstract

Abstract Introduction In the dopamine system, the mesolimbic pathway, including the dorsal striatum, underlies the reinforcing properties of tobacco smoking, and the mesocortical pathway, including the dorsolateral prefrontal cortex (dlPFC), is critical for cognitive functioning. Dysregulated dopamine signaling has been linked to drug-seeking behaviors and cognitive deficits. The dorsal striatum and dlPFC are structurally and functionally connected and are key regions for cognitive functioning. We recently showed that people who smoke have lower dlPFC dopamine (D2/3R) receptor availability than people who do not, which is related to poorer cognitive function. Aims and Methods The goal of this study was to examine the same brain-behavior relationship in the dorsal striatum. Twenty-nine (18 males) recently abstinent people who smoke and 29 sex-matched healthy controls participated in 2 same-day [11C]-(+)-PHNO positron emission tomography scans before and after amphetamine administration to provoke dopamine release. D2/3R availability (binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND) were calculated. Cognition (verbal learning and memory) was assessed with the CogState computerized battery. Results There were no group differences in baseline BPND. People who smoke have a smaller magnitude %ΔBPND in dorsal putamen than healthy controls (p = .022). People who smoke perform worse on immediate (p = .035) and delayed (p = .011) recall than healthy controls. In all people, lower dorsal putamen BPND was associated with worse immediate (p = .006) and delayed recall (p = .049), and lower %ΔBPND was related to worse delayed recall (p = .022). Conclusions Lower dorsal putamen D2/3R availability and function are associated with disruptions in cognitive function that may underlie difficulty with resisting smoking. Implications This study directly relates dopamine imaging outcomes in the dorsal striatum to cognitive function in recently abstinent people who smoke cigarettes and healthy controls. The current work included a well-characterized subject sample in terms of demographics, smoking characteristics, and a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature relating dopamine imaging outcomes to cognition in recently abstinent people who smoke and people who do not smoke, expanding our understanding of brain-behavior relationships.