The relationship between α4β2-nicotinic acetylcholine receptor availability and brain arousal regulation as assessed by 2-[18F]F-A85380 PET and EEG following nicotine cessation in male individuals with nicotine dependence

BACKGROUND: While α4β2-nicotinic-acetylcholine-receptor (α4β2-nAChR) density has been linked to cognitive performance, it remains unclear whether nicotine's cognitive-enhancing effect are mediated primarily through direct receptor action. An alternative view suggests that nicotine exerts its influence by stabilizing brain arousal, which can be assessed using electroencephalography (EEG). This study examines the relationship between changes in α4β2-nAChR availability and brain arousal regulation following nicotine cessation in nicotine-dependent males. METHODS: Ten nicotine-dependent male participants underwent assessments during continued smoking, 24-h, and 7-day nicotine cessation in counterbalanced sequences. The α4β2-nAChR availability was measured using positron emission tomography (PET) under continued smoking and after 7-day nicotine cessation. EEG-based algorithm assessed changes in brain arousal regulation. RESULTS: A 7-day nicotine cessation led to higher availability of α4β2-nAChR in male participants. Despite higher availability of α4β2-nAChR, nicotine cessation showed no significant effect on arousal stability score and EEG-vigilance score. The findings of exploratory analyses suggested a potential non-linear relationship between α4β2-nAChR availability and arousal regulation. CONCLUSION: The findings may suggest that the brain arousal regulation in some of the male participants may become more instable following a 7-day smoking cessation despite increased α4β2-nAChR binding. However, this sample limits the generalizability, and further studies with larger cohorts are needed.