The β4 nicotinic receptor subunit modulates the chronic antidepressant effect mediated by bupropion

The objective of the current study is to investigate the role of the nicotinic receptor β4 subunit in the antidepressant activity of bupropion. Wild-type (β4+/+) and knockout (β4−/−) mice were intraperitoneally administered with normal saline (control) or bupropion (40 mg/kg) daily for the first two weeks. Forced swim tests were performed on day 1 to determine the acute effect of bupropion at 0, 15, 30, 45, or 60 min after the injection, and after two weeks of daily treatment to determine the chronic effects. To examine the remnant effects of bupropion after withdrawal, forced swim tests were performed one and two weeks after the last day of treatment with bupropion. Our results indicate that: (1) the acute treatment with bupropion increases the swimming time (i.e., antidepressant effect) in β4+/+ and β4−/− mice from both genders, (2) the antidepressant effect after the chronic treatment is seen only in female β4+/+ mice, and (3) the residual antidepressant effect of bupropion persists only in male β4+/+ mice after one week withdrawal. We conclude that the β4 subunit plays a modulatory role in the chronic antidepressant effect mediated by bupropion, and that its effect is gender-specific.