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Nicotine and Tobacco as Gateway Drugs Key findings on nicotines gateway mechanisms include: Kandel and Kandel (2014), in a landmark New England Journal of Medicine paper, demonstrated that nicotine acts as a gateway drug through a specific epigenetic mechanism: inhibition of HDAC enzymes in the striatum increases histone H3 and H4 acetylation at the FosB gene promoter, amplifying cocaines rewarding effects through a pathway distinct from nicotines direct pharmacological action

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