Journal
GENES BRAIN AND BEHAVIOR
Volume 15, Issue 1, Pages 89-107Publisher
WILEY
DOI: 10.1111/gbb.12251
Keywords
CHRN genes; comorbid drug use; developmental changes and nAChRs; nicotine-induced receptor upregulation; review
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Funding
- NIAAA NIH HHS [R01 AA017889, T32 AA013525] Funding Source: Medline
- NIDA NIH HHS [R21 DA036673, T32 DA017637] Funding Source: Medline
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Nicotinic acetylcholine receptors are ligand-gated ion channels that exogenously bind nicotine. Nicotine produces rewarding effects by interacting with these receptors in the brain's reward system. Unlike other receptors, chronic stimulation by an agonist induces an upregulation of receptor number that is not due to increased gene expression in adults; while upregulation also occurs during development and adolescence there have been some opposing findings regarding a change in corresponding gene expression. These receptors have also been well studied with regard to human genetic associations and, based on evidence suggesting shared genetic liabilities between substance use disorders, numerous studies have pointed to a role for this system in comorbid drug use. This review will focus on upregulation of these receptors in adulthood, adolescence and development, as well as the findings from human genetic association studies which point to different roles for these receptors in risk for initiation and continuation of drug use.
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