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

• Published in: Psychiatry research. Neuroimaging Vol. 352; p. 112035
• Main Authors: Huang, Jue, Meyer, Philipp M., Guerrero, Ivonne Burgos, Becker, Georg A., Rullmann, Michael, Mauche, Nicole, Sattler, Bernhard, Hesse, Swen, Zientek, Franziska R., Hegerl, Ulrich, Strauß, Maria, Sabri, Osama
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2025
• Subjects: 2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A85380); Adult; Arousal - drug effects; Arousal - physiology; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Brain arousal; EEG; Electroencephalography; Humans; Male; Middle Aged; Nicotine; Nicotine cessation; PET; Positron-Emission Tomography; Receptors, Nicotinic - metabolism; Smoking Cessation; Tobacco Use Disorder - diagnostic imaging; Tobacco Use Disorder - metabolism; Tobacco Use Disorder - physiopathology; α4β2-nAChR; Brain arousal; Nicotine cessation; 2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A85380); EEG; PET; α4β2-nAChR; 2-[F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[F]F-A85380)
• ISSN: 0925-4927; 1872-7506; 1872-7506
• DOI: 10.1016/j.pscychresns.2025.112035

•PET scan recorded changes in α4β2-nAChR availability after smoking cessation.•EEG recorded changes in CNS arousal regulation after smoking cessation.•Observed increase in α4β2-nAChR availability after smoking cessation.•The decreased CNS arousal regulation lacked statistical significance.•Observed increase in α4β2-nAChR availability did not correlate with arousal changes. 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. 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. 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. 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.