2025-06-05
Tobacco: a deeper addiction than it seems
Pharmacology and Toxicology Addictology
#Tobacco #Nicotine
#Addiction #Epigenetics #DNA
Tobacco remains one of the greatest contemporary public health scourges, responsible for over 8 million deaths every year. Despite growing awareness of the dangers of smoking, nicotine addiction proves to be highly persistent. This phenomenon is partly explained by nicotine’s powerful action on the reward system. But beyond these immediate effects, recent research reveals a far more lasting impact.
Nicotine modifies the expression of genes involved in learning and memory through epigenetic mechanisms. This long-term reprogramming contributes to the deeply rooted nature of the addiction.
Nicotine primarily acts on nicotinic acetylcholine receptors (nAChRs), which are found in brain areas involved in memory and pleasure: the hippocampus, prefrontal cortex, and ventral tegmental area. This activation triggers a cascade of biological processes that facilitate the encoding of tobacco-related memories.
One of the most well-documented effects of nicotine is the increase in histone acetylation, particularly H3 and H4. This chemical modification "opens" the chromatin structure, making key genes more accessible, such as FosB, BDNF (Brain-Derived Neurotrophic Factor), and DRD1 (Dopamine D1 receptor)—all associated with reward, learning, and memory consolidation.
Simultaneously, nicotine reduces certain repressive methylation marks, like H3K9me2 and H3K27me3, especially in the promoters of the BDNF and CDK5 genes. The result is increased expression of these genes, promoting the formation of persistent consumption-related memories and contributing to relapse, even after extended abstinence.
Nicotine also influences DNA methylation, another form of epigenetic regulation. In smokers, hypomethylation of several genes has been observed—especially those encoding the nicotinic receptors CHRNA3, CHRNA5, and CHRNB4—thereby increasing nicotine sensitivity and vulnerability to addiction. These changes may constitute an epigenetic “priming” mechanism.
Finally, nicotine modulates the expression of numerous microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which play a central role in post-transcriptional regulation. For example, miR-221 amplifies behavioral sensitivity to nicotine, while the antisense lncRNA of BDNF is involved in the consolidation and maintenance of dependence.
Tobacco dependence is not merely the result of short-lived effects. Nicotine induces profound and lasting changes in the expression of genes associated with memory and reward. These epigenetic modifications—including histone acetylation, demethylation, and non-coding RNA regulation—help inscribe addiction into the very biology of the brain. Understanding these mechanisms opens promising therapeutic avenues: targeting the epigenome to erase the traces left by nicotine and promote lasting detoxification.
Tobacco remains one of the greatest contemporary public health scourges, responsible for over 8 million deaths every year. Despite growing awareness of the dangers of smoking, nicotine addiction proves to be highly persistent. This phenomenon is partly explained by nicotine’s powerful action on the reward system. But beyond these immediate effects, recent research reveals a far more lasting impact.
Nicotine modifies the expression of genes involved in learning and memory through epigenetic mechanisms. This long-term reprogramming contributes to the deeply rooted nature of the addiction.
1. Nicotine and brain plasticity: fertile ground for epigenetic imprinting
Nicotine primarily acts on nicotinic acetylcholine receptors (nAChRs), which are found in brain areas involved in memory and pleasure: the hippocampus, prefrontal cortex, and ventral tegmental area. This activation triggers a cascade of biological processes that facilitate the encoding of tobacco-related memories.
2. Histone acetylation: unlocking addiction genes
One of the most well-documented effects of nicotine is the increase in histone acetylation, particularly H3 and H4. This chemical modification "opens" the chromatin structure, making key genes more accessible, such as FosB, BDNF (Brain-Derived Neurotrophic Factor), and DRD1 (Dopamine D1 receptor)—all associated with reward, learning, and memory consolidation.
3. Lifting the brakes: histone demethylation
Simultaneously, nicotine reduces certain repressive methylation marks, like H3K9me2 and H3K27me3, especially in the promoters of the BDNF and CDK5 genes. The result is increased expression of these genes, promoting the formation of persistent consumption-related memories and contributing to relapse, even after extended abstinence.
Read next: Breathing can kill—even without smoking.
4. Nicotine’s mark on DNA
Nicotine also influences DNA methylation, another form of epigenetic regulation. In smokers, hypomethylation of several genes has been observed—especially those encoding the nicotinic receptors CHRNA3, CHRNA5, and CHRNB4—thereby increasing nicotine sensitivity and vulnerability to addiction. These changes may constitute an epigenetic “priming” mechanism.
5. Non-coding RNAs: the silent conductors
Finally, nicotine modulates the expression of numerous microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which play a central role in post-transcriptional regulation. For example, miR-221 amplifies behavioral sensitivity to nicotine, while the antisense lncRNA of BDNF is involved in the consolidation and maintenance of dependence.
Toward an epigenetic memory of addiction
Tobacco dependence is not merely the result of short-lived effects. Nicotine induces profound and lasting changes in the expression of genes associated with memory and reward. These epigenetic modifications—including histone acetylation, demethylation, and non-coding RNA regulation—help inscribe addiction into the very biology of the brain. Understanding these mechanisms opens promising therapeutic avenues: targeting the epigenome to erase the traces left by nicotine and promote lasting detoxification.
Read next: Smoke less, think better?
Last press reviews
Binge eating: when neurons crave food
#EatingDisorder #BingeEating #AnimalModels #Anxiety #Compulsivity #Meta...
Binge eating under high tension
#BED #ED #rTMS #Neuromodulation #Craving #InhibitoryControl ...