Study shows nicotine's varied effects on brain's reward and aversion centers

A new study, led by researchers at the Marshall University Joan C. Edwards School of Medicinehighlight the intricate interplay of brain regions involved in nicotine's effects on the human brain.

The study, published in the open-access journal eNeuro by the Society for Neuroscience, examines nicotine's complex effects on brain regions tied to reward and aversion. It highlights the nuanced interaction that is influenced by factors like dosage, the presence of additives such as menthol, and the sex of the individual. The focus is on the medial habenula (MHb), critical for nicotine aversion, where researchers observed variable activity levels based on these factors. This variability contrasts with the behaviour in reward-related areas such as the ventral tegmental area, offering new insights into nicotine's differential impact on the brain.

"This study demonstrates that the activity of crucial brain regions associated with nicotine dependence is altered in different ways based on nicotine dosage and sex,” said lead researcher Nathan Olszewski, a biomedical research doctoral student at Marshall University in the laboratory of Brandon J. Henderson, Ph.D. “Nicotine usage affects individuals uniquely, making it advisable for users to exercise caution."

The study employed a method where mice inhaled nicotine vapor by poking their noses into a device, mimicking how humans might self-administer nicotine. The researchers used advanced techniques to study how nicotine affects nerve cell activity in two brain areas, the medial habenula and the ventral tegmental area, looking at differences based on the amount of nicotine and whether the mice were male or female. They also measured how nicotine changed the release of dopamine, a chemical related to pleasure, in another part of the brain called the nucleus accumbens.

The researchers plan to broaden their study to include additional brain areas, especially looking at the connection between the medial habenula (MHb) and the interpeduncular nucleus (IPN). This pathway is key for controlling nicotine consumption and managing withdrawal symptoms. Further research will use techniques like electrophysiology, confocal microscopy, and RNA-fluorescent in situ hybridization (FISH) to explore how nicotine impacts the behaviour and levels of nicotinic acetylcholine receptors within this critical circuit.

"In our field, attention has predominantly focused on specific regions like the ventral tegmental area,” said Henderson, an associate professor of biomedical sciences at Marshall University. “This study underscores the necessity of exploring other brain areas controlling the negative aspects of nicotine exposure."

Reference: “Neuronal excitability in the medial habenula and ventral tegmental area is differentially modulated by nicotine dosage and menthol in a sex-specific manner”DOI: 10.1523/ENEURO.0380-23.2024