Journal Article

Acute nicotine abstinence amplifies subjective withdrawal symptoms and threat-evoked fear and anxiety, but not extended amygdala reactivity

Smith, Jason F., Islam, Samiha, Shackman, Alexander J., Anderson, Allegra S., Curtin, John J., DeYoung, Kathryn A., Piper, Megan E., Kim, Hyung Cho, Kaplan, Claire M., Fox, Andrew S., Bradford, Daniel E.

2023

Overview

Tobacco smoking imposes a staggering burden on public health, underscoring the urgency of developing a deeper understanding of the processes that maintain addiction. Clinical and experience-sampling data highlight the importance of anxious withdrawal symptoms, but the underlying neurobiology has remained elusive. Mechanistic work in animals implicates the central extended amygdala (EAc)—including the central nucleus of the amygdala and the neighboring bed nucleus of the stria terminalis—but the translational relevance of these discoveries remains unexplored. Here we leveraged a randomized trial design, well-established threat-anticipation paradigm, and multidimensional battery of assessments to understand the consequences of 24-hour nicotine abstinence. The threat-anticipation paradigm had the expected consequences, amplifying subjective distress and arousal, and recruiting the canonical threat-anticipation network. Abstinence increased smoking urges and withdrawal symptoms, and potentiated threat-evoked distress, but had negligible consequences for EAc threat reactivity, raising questions about the translational relevance of prominent animal and human models of addiction. These observations provide a framework for conceptualizing nicotine abstinence and withdrawal, with implications for basic, translational, and clinical science.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abstinence / Addictions / Amplification / Amygdala / Amygdala - physiology / Animal models / Anxiety / Arousal / Biology and Life Sciences / Carbon monoxide / Drug withdrawal symptoms / Emotions / Fear - physiology / Health aspects / Humans / Hypotheses / Hypothesis testing / Magnetic resonance imaging / Medical imaging / Medicine and Health Sciences / Methods / Nervous system / Neurobiology / Neuroimaging / Neurophysiology / Nicotine / Nicotine - adverse effects / Physical Sciences / Public health / Questionnaires / Research and Analysis Methods / Risk factors / Rodents / Septal Nuclei - physiology / Smoking / Smoking cessation programs / Social Sciences / Stria terminalis / Substance Withdrawal Syndrome / Tobacco / Tobacco smoking / Translation / Withdrawal