Effects of bupropion on nicotine withdrawal associated disturbances in circulating corticosterone and brain 5-HT turnover in mice

Bupropion (Bup), an antidepressant, is used to treat depression and aid in quitting smoking. We aim to investigate the influence of Bup on nicotine withdrawal (NW)-associated disturbances in serotonergic neurotransmission and behavior in mice. Adult albino mice were categorized into control and NW groups. Each group was further divided into saline and Bup-administered (n=6/group). NW groups received nicotine at a concentration of 3.08 mg (equivalent to 1 milligram of free base) in 100 ml of tap water for four weeks, while the control group received nicotine-free water. To induce nicotine withdrawal, the nicotine-containing water was substituted with tap water for 72 hours. Bup (20 mg/kg) and saline were administered (i.p.) three hours before the completion of the 72-hour withdrawal period to the test and control groups, respectively. NW signs were monitored in both groups. Bup-treated NW mice demonstrated a decline in corticosterone levels while concurrently exhibiting an increase in 5-HT synthesis with decreased 5-HT turnover compared to NW saline controls. A positive correlation between plasma corticosterone and 5-HT turnover was also found in Bup-administered NW mice. Taken together, Bup has potential therapeutic effects on nicotine withdrawal-associated somatic signs due to its ability to attenuate 5-HT turnover and plasma corticosterone in dependent mice.