A new study led by researchers at the Joan C. Edwards School of Medicine at Marshall University sheds light on the intricate interplay of brain regions involved in the effects of nicotine on the human brain.
The research, published in eNeuro, an open-access, peer-reviewed scientific journal published by the Society for Neuroscience, explores how nicotine influences key areas associated with reward and aversion, showing a nuanced relationship that varies by dose, sex, and different regions. of the brain. The medial habenula (MHb), a region known to regulate nicotine aversion, takes center stage in the study. The researchers found that MHb activity undergoes fluctuations, either increased or decreased, depending on factors such as the amount of nicotine consumed, dosage variations (with or without menthol), and the sex of the subject. Interestingly, this modulation was not reflected in reward centers such as the ventral tegmental area, challenging previous assumptions about the impact of nicotine.
“This study demonstrates that the activity of crucial brain regions associated with nicotine dependence is altered in different ways depending on nicotine dose and sex,” said lead researcher Nathan Olszewski, a doctoral student in biomedical research at the University Marshall in the laboratory of Brandon J. Henderson. , Doctor. “Nicotine use uniquely affects individuals, so users are advised to exercise caution.”
The study employed a vapor inhalation model of nicotine self-administration in mice, puncturing the nose to obtain deliveries of nicotine vapor. Employing patch clamp electrophysiology, the researchers elucidated changes in neuronal excitability in the medial habenula and ventral tegmental area depending on nicotine dose and sex. Fast scan cyclic voltammetry was also used to assess changes in dopamine release dynamics in the nucleus accumbens.
“In our field, attention has been predominantly focused on specific regions such as the ventral tegmental area,” said Henderson, an associate professor of biomedical sciences at Marshall University. “This study highlights the need to explore other areas of the brain that control the negative aspects of nicotine exposure.”
The researchers aim to expand their research to other regions of the brain, focusing especially on the interaction between the MHb and the interpeduncular nucleus (IPN). This circuit, known as the nicotine aversive pathway, plays a crucial role in limiting nicotine intake and withdrawal symptoms. Future research will use electrophysiology, confocal microscopy, and RNA fluorescence in situ hybridization (FISH) to understand how nicotine alters the activity and expression of nicotinic acetylcholine receptors in this aversive circuit.
In addition to Olszewski and Henderson, Samuel Tetteh-Quarshie, another Ph.D. student in Henderson's lab, is a co-author of the study. This study was funded by a grant (#DA050717 to Henderson) from the National Institute on Drug Abuse (NIDA).