#South Korea #Pusan National University #Busan #Glial Cells #Nicotine Addiction

Uncovering Addiction Mechanisms: The Role of Astrocytes in Nicotine Dependency

Nicotine addiction remains a formidable public health challenge, with millions struggling to quit across the globe. Traditional research has predominantly focused on neurons, overlooking the significant role that other brain cells, particularly astrocytes, may play in addictive behaviors. Recent findings from a team at Pusan National University, led by Professor Eun Sang Choe, shine a spotlight on the critical involvement of astrocytic glutamine synthetase (GS) in the mechanisms of nicotine addiction, opening new avenues for potential interventions.

The study, published in the journal Acta Pharmaceutica Sinica B on September 25, 2025, reveals that GS, an enzyme found in astrocytes—supportive cells in the brain long considered passive—actively regulates the brain's response to nicotine. The researchers discovered that repeated nicotine exposure leads to changes in astrocytes, which subsequently initiate significant changes in neuronal behavior associated with addiction. This perspective shift underscores how essential these glial cells are to the brain's reward pathways and addiction processes.

To conduct the study, the research team carried out a series of experiments on rat models. They injected nicotine repeatedly and observed the stimulation of α7 nicotinic acetylcholine receptors on astrocytes situated in critical brain regions such as the caudate and putamen. This stimulation triggered an increase in intracellular calcium levels, which subsequently activated phosphorylated c-Jun N-terminal kinase (pJNK), a molecule known for its response to cellular stress and drug exposure.

Probing deeper, the activated pJNK was found to interact with the metabotropic glutamate receptor 1a (mGluR1a), leading to increased GS activity and altered glutamate signaling pathways. This process culminated in enhanced locomotor sensitization, a behavior indicative of increased drug seeking due to repeated nicotine exposure.

To validate their findings, the researchers engineered a specific inhibitory peptide that blocked the interaction between pJNK and mGluR1a. Administering this peptide to the rat models resulted in a significant reduction of GS activity and a decrease in locomotor sensitization. This pivotal observation highlights the role of astrocytes in modulating brain function in response to nicotine and suggests that interventions targeting astrocytic signaling might help mitigate nicotine dependence.

While these findings are preclinical, the implications are far-reaching. The recognition of astrocytes as active participants in nicotine addiction offers potential for developing comprehensive smoking cessation strategies. Professor Choe emphasizes that while direct human application awaits further exploration, this research paves the way for new therapeutic approaches that could support individuals striving to overcome nicotine dependence.

In conclusion, the Pusan National University study not only unearths the involvement of astrocytes in nicotine addiction but also challenges the long-standing neuron-centric perspective of addiction research. By illuminating these mechanisms, researchers are one step closer to creating effective treatments that tackle one of the most stubborn public health issues of our time.

Reference

Original paper: Glutamine synthetase in astrocytes of the caudate and putamen is responsible for locomotor sensitization after nicotine exposure
Journal: Acta Pharmaceutica Sinica B
DOI: 10.1016/j.apsb.2025.09.038