Drug Addiction: Mechanisms of Nicotine Dependence Unmasked by Gene Editing

The rs16969968 SNP in CHRNA5 gene influences vulnerability to nicotine addiction (impacts the function of a5* nicotinic acetylcholine receptors or nAchRs rather than altering expression, increasing the amount of nicotine consumed and motivation to seek out the drug without altering responsiveness in VTA) and relapse (by reducing recruitment of the interpedencular nucleus). This paper discusses mainly findings by Forget et al. (2018) who used a gene editing technique to study nicotine addiction. I found the paper informative, but I feel it could have more clarity. The switching between mouse and rat experiments was confusing at times and there was not always clear demarcation of complete Chrna5 ablation vs. presence of the rs16969968 SNP in Chrna5. There was not a lot of in depth exploration of the methods used in the paper (for example: "Forget et al. therefore determined whether the actions of nicotine on ventral tegmental area neurons were altered in the a5 subunit mutant rats." How? Techniques are not even mentioned). I appreciated the discussion about specifically modifying genes rather than completely removing them to investigate neuropsychiatric disease.

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