Major depressive disorder (MDD) is a serious mental illness that affects millions of people
worldwide. There is now compelling evidence that the neuronal nicotinic acetylcholine receptors
(nAChRs) play an important role in MDD and co-morbid alcohol or nicotine addiction. As a result,
there has been growing interest for the treatment of MDD and co-morbid alcohol or nicotine use
disorder by targeting nAChRs. Emerging evidence suggests that specific ligands that act at nAChRs
significantly reduce depression-like behaviors in preclinical models that mimic MDD and co-morbid
alcohol or nicotine use disorder. In this review, the pharmacological efficacy of nAChR ligands, such
as mecamylamine, lobeline, cytisine, sazetidine-A, and others will be discussed. Overall, findings from preclinical and
clinical studies included here suggest that the nAChR ligands may be of potential benefit in reducing MDD symptoms and
that may aid in the prevention and treatment of MDD and co-morbid alcohol or nicotine use disorder.
Keywords: Alcohol use disorder, antidepressant, comorbidity, drug addiction, drug discovery, major depressive disorder, mood
disorder, nicotinic receptor, nicotine use disorder.
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