New research has revealed that astrocytes—brain glial cells once thought to be passive—actively contribute to nicotine-induced changes that reinforce addiction. The study, led by Professor Eun Sang Choe at Pusan National University in South Korea, shows that astrocytic glutamine synthetase (GS) regulates locomotor sensitization after repeated nicotine exposure, highlighting a previously overlooked mechanism in the brain’s reward system.
Using rat models, the team found that nicotine activated α7 nicotinic acetylcholine receptors on astrocytes in the caudate and putamen, triggering intracellular calcium surges. This led to activation of phosphorylated c-Jun N-terminal kinase (pJNK), which interacted with metabotropic glutamate receptor 1a (mGluR1a) to boost GS activity and the glutamate-glutamine pathway, enhancing locomotor sensitization. Blocking this pathway with a custom inhibitory peptide reduced GS activity and dampened nicotine-induced behavioral changes.
The findings underscore the importance of neuron-glia communication in addiction and offer new directions for research into nicotine dependence. While clinical applications remain distant, Professor Choe says the study “deepens our understanding of nicotine addiction, paving the way for development of therapeutic strategies to support smoking-cessation efforts.”
