This 2018 US government rodent study used extreme dosages to achieve its directed goals of demonizing nicotine and extolling the biomarker paradigm:
“This study examined whether adolescent nicotine exposure alters adult hippocampus-dependent learning, involving persistent changes in hippocampal DNA methylation and if choline, a dietary methyl donor, would reverse and mitigate these alterations.
Mice were chronically treated with nicotine (12.6mg/kg/day) starting at post-natal day 23 (pre-adolescent), p38 (late adolescent), or p54 (adult) for 12 days followed by a 30-day period during which they consumed either standard chow or chow supplemented with choline (9g/kg).
Our gene expression analyses support this model and point to two particular genes involved in chromatin remodeling, Smarca2 and Bahcc1. Both Smarca2 and Bahcc1 showed a similar inverse correlation pattern between promoter methylation and gene expression.
Our findings support a role for epigenetic modification of hippocampal chromatin remodeling genes in long-term learning deficits induced by adolescent nicotine and their amelioration by dietary choline supplementation.”
Let’s use the average weight of a US adult male, which is published by the US Centers for Disease Control at 88.8 kg, to compare dosages:
- Nicotine at “12.6mg/kg/day” x 88.8 = 1119 mg, The estimated lower limit of a lethal dose of nicotine has been reported as between 500 and 1000 mg!
- Choline at “9g/kg” x 88.8 = 799 g. The US National Institutes of Health published the Tolerable Upper Intake Levels for Choline as 3.5 g!
A funding source of this study was National Institute on Drug Abuse (NIDA) Identification of Biomarkers for Nicotine Addiction award (T-DA-1002 MG). Is the biomarker paradigm institutionalized to the point where studies that don’t have biomarkers as goals aren’t funded?
Is the main purpose of animal studies to help humans? Or is it to promote an agenda?
https://www.sciencedirect.com/science/article/pii/S107474271830193X “Choline ameliorates adult learning deficits and reverses epigenetic modification of chromatin remodeling factors related to adolescent nicotine exposure” (not freely available)