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Linking the CHRNA5 SNP to drug abuse liability: From circuitry to cellular mechanisms

Journal

NEUROPHARMACOLOGY
Volume 186, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2021.108480

Keywords

Substance abuse; Nicotinic acetylcholine receptor; Single nucleotide polymorphism; Mice; Neuroimaging

Funding

  1. National Institute on Drug Abuse [R01-DA041180, T32-DA028874]

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Genetics, specifically the SNP D398N in the CHRNA5 gene, has been linked to addiction to various substances including nicotine, opioids, cocaine, and alcohol. Studies in humans, rodents, and cell lines suggest that this SNP broadly influences response to drugs of abuse in a non-substance-specific manner, shedding light on the role of the cholinergic system in reward and addiction vulnerability.
Genetics are known to be a significant risk factor for drug abuse. In human populations, the single nucleotide polymorphism (SNP) D398N in the gene CHRNA5 has been associated with addiction to nicotine, opioids, cocaine, and alcohol. In this paper, we review findings from studies in humans, rodent models, and cell lines and provide evidence that collectively suggests that the Chrna5 SNP broadly influences the response to drugs of abuse in a manner that is not substance-specific. This finding has important implications for our understanding of the role of the cholinergic system in reward and addiction vulnerability.

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