Pathophysiology of nAChRs: Limbic circuits and related disorders

Human epidemiological studies have identified links between nicotine intake and stress disorders, including anxiety, depression and PTSD. Here we review the clinical evidence for activation and desensitization of nicotinic acetylcholine receptors (nAChRs) relevant to affective disorders. We go on to describe clinical and preclinical pharmacological studies suggesting that nAChR function may be involved in the etiology of anxiety and depressive disorders, may be relevant targets for medication development, and may contribute to the antidepressant efficacy of non-nicotinic therapeutics. We then review what is known about nAChR function in a subset of limbic system areas (amygdala, hippocampus and prefrontal cortex), and how this contributes to stressrelevant behaviors in preclinical models that may be relevant to human affective disorders. Taken together, the preclinical and clinical literature point to a clear role for ACh signaling through nAChRs in regulation of behavioral responses to stress. Disruption of nAChR homeostasis is likely to contribute to the psychopathology observed in anxiety and depressive disorders. Targeting specific nAChRs may therefore be a strategy for medication development to treat these disorders or to augment the efficacy of current therapeutics.

Automated summary

Human epidemiological studies have found a connection between nicotine intake and stress disorders such as anxiety, depression, and PTSD. This article reviews the clinical evidence for the activation and desensitization of nicotinic acetylcholine receptors (nAChRs) in relation to affective disorders. It also discusses how nAChR function may contribute to anxiety and depressive disorders, making them potential targets for medication development. The article further explores the role of nAChR in limbic system areas and its impact on stress-related behaviors that are relevant to human affective disorders.