Nicotine’s Influence on Reward and Aversion

Summary: A new study delves into how nicotine influences the brain, revealing its complex effects on areas related to reward and aversion. Focusing on the medial habenula, researchers found its activity varies significantly with nicotine dosage, presence of menthol, and the subject’s sex, a discovery that challenges previous understanding of nicotine’s uniform impact on reward pathways.

Utilizing advanced techniques like patch-clamp electrophysiology and fast-scan cyclic voltammetry, the study offers new insights into nicotine’s nuanced relationship with the brain, emphasizing the importance of considering individual differences in nicotine addiction research.

Key Facts:

  1. The study highlights how nicotine’s effects on the brain are influenced by dosage, menthol presence, and sex, particularly in the medial habenula, a region associated with nicotine aversion.
  2. Unlike assumed uniform effects on reward centers like the ventral tegmental area, the MHb shows varied activity, underscoring nicotine’s complex influence on brain function.
  3. Future research aims to explore the aversive pathway of nicotine usage further, focusing on the interaction between the MHb and the interpeduncular nucleus to understand withdrawal symptoms and intake limitations.

Source: Marshall University

A new study led by researchers at the Marshall University Joan C. Edwards School of Medicine sheds light on the intricate interplay of brain regions involved in nicotine’s effects 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, showcasing a nuanced relationship that varies based on dosage, sex and distinct brain regions.

This shows a brain surrounded by smoke.
The study employed a vapor-inhalation model of nicotine self-administration in mice, utilizing nose poking to earn nicotine vapor deliveries. Credit: Neuroscience News

The medial habenula (MHb), a region known for regulating nicotine aversion, takes center stage in the study. Researchers discovered that MHb activity experiences fluctuations, either heightened or diminished, depending on factors such as the amount of nicotine consumed, dosage variations (with or without menthol), and the sex of the subject. Intriguingly, this modulation was not mirrored in reward centers like the ventral tegmental area, challenging previous assumptions about nicotine’s impact.

“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 vapor-inhalation model of nicotine self-administration in mice, utilizing nose poking to earn nicotine vapor deliveries. Employing patch-clamp electrophysiology, researchers elucidated changes in neuronal excitability in the medial habenula and ventral tegmental area based on nicotine dosage 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 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.”

The researchers aim to expand their investigation to other brain regions, particularly focusing on the interplay between the MHb and the interpeduncular nucleus (IPN). This circuit, known as the aversive pathway of nicotine usage, plays a crucial role in limiting nicotine intake and withdrawal symptoms.

Future research will utilize electrophysiology, confocal microscopy and RNA-fluorescent in situ hybridization (FISH) to understand how nicotine alters the activity and expression of nicotinic acetylcholine receptors in this aversive circuit.

Funding: In addition to Olszewski and Henderson, Samuel Tetteh-Quarshie, another Ph.D. student in the Henderson laboratory, is a co-author on the study. This study was supported with grant funding (#DA050717 to Henderson) from the National Institute on Drug Abuse (NIDA).

About this neuroscience and nicotine research news

Author: Sheanna Spence
Source: Marshall University
Contact: Sheanna Spence – Marshall University
Image: The image is credited to Neuroscience News

Original Research: Open access.
Neuronal Excitability in the Medial Habenula and Ventral Tegmental Area Is Differentially Modulated by Nicotine Dosage and Menthol in a Sex-Specific Manner” by Nathan Olszewski et al. eNeuro


Neuronal Excitability in the Medial Habenula and Ventral Tegmental Area Is Differentially Modulated by Nicotine Dosage and Menthol in a Sex-Specific Manner

The medial habenula (MHb) has been identified as the limiting factor for nicotine intake and facilitating nicotine withdrawal.

However, few studies have assessed MHb neuronal excitability in response to nicotine, and, currently, a gap in knowledge is present for finding behavioral correlates to neuronal excitability in the region. Moreover, no study to date has evaluated sex or nicotine dosage as factors of excitability in the MHb.

Here, we utilized an e-vape self-administration (EVSA) model to determine differences between sexes with different nicotine dosages ± menthol. Following this paradigm, we employed patch-clamp electrophysiology to assess key metrics of MHb neuronal excitability in relation to behavioral endpoints.

We observed female mice self-administered significantly more than males, regardless of dosage. We also observed a direct correlation between self-administration behavior and MHb excitability with low-dose nicotine + menthol in males.

Conversely, a high dose of nicotine ± menthol yields an inverse correlation between excitability and self-administration behavior in males only. In addition, intrinsic excitability in the ventral tegmental area (VTA) does not track with the amount of nicotine self-administered.

Rather, they correlate to the active/inactive discrimination of mice. Using fast-scan cyclic voltammetry, we also observed that dopamine release dynamics are linked to reinforcement-related behavior in males and motivation-related behaviors in females.

These results point to a sex-specific difference in the activity of the MHb and VTA leading to distinct differences in self-administration behavior. His could lend evidence to clinical observations of smoking and nicotine-use behavior differing between males and females.

Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.
We hate spam and only use your email to contact you about newsletters. You can cancel your subscription any time.