Transcriptomic Analysis Reveals Differential Gene Expression in the Mouse Medial Habenula During Nicotine Withdrawal

Negative emotion during smoking cessation is a major obstacle to successful quitting, yet the underlying molecular mechanisms remain poorly understood. Nicotine withdrawal induces profound transcriptional alterations in brain regions associated with affective processing, prompting us to investigate their contribution to withdrawal-induced negative emotional states. Here, by performing transcriptomic sequencing of the ventral medial habenula (MHb) in a mouse model of nicotine withdrawal, we found that calcium channel–related genes were markedly upregulated. Further analysis revealed a concomitant downregulation of the RNA-binding protein Pumilio 1 (Pum1), which acts to suppress calcium channel expression. Together, these findings identify a Pum1–calcium channel regulatory axis that may underlie nicotine withdrawal–induced negative affect.