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. Overall design: Six wild-type mice were administered nicotine ditartrate (4 mg/kg, intraperitoneally) twice daily for 14 consecutive days. On day 15, nicotine injections were replaced with saline to induce nicotine withdrawal, and these mice were assigned to the experimental group (designated as the nicotine group for transcriptomic analysis). In parallel, four wild-type mice received intraperitoneal injections of saline for 17 consecutive days and served as the control group (designated as the control group). On day 17, medial habenula (MHb) brain tissue was collected from mice in both groups for transcriptomic sequencing, and differential gene expression was analyzed.