LAUSR

HIGHLIGHTSRole of nicotinic receptors was tested in the antidepressant effects of bupropion.&agr;4, &agr;5, &agr;6, and &bgr;2 nicotinic receptor subunit WT&KO mice were studied using the FST.&agr;4, &agr;6, and &bgr;2 subunits modulate the antidepressant‐like effects of bupropion. ABSTRACT The objective of the present study is to investigate the role of &agr;4, &agr;5, &agr;6 or &bgr;2 nAChR subunits in the antidepressant‐like effect of bupropion. Adult male mice were treated with subcutaneous acute doses of bupropion (3 and 10 mg/kg) 30 min before the forced swim test (FST) in &agr;4, &agr;5, &agr;6, or &bgr;2 nAChR subunit knockout (KO) and wild‐type (WT) mice. In addition, the effects of &bgr;2* antagonist dihydro‐&bgr;‐erythroidine (DH&bgr;E, 3 mg/kg) on antidepressant‐like effects of bupropion in C57BL/6 J mice were assessed. Our results showed that baseline immobility and climbing time did not differ between KO and corresponding WT mice except for &bgr;2 KO. Bupropion significantly decreased immobility time and increased climbing time in the &agr;4, &agr;6 and &bgr;2 nAChR KO mice in comparison to WT littermates, indicating that lack of these nAChR subunits enhanced antidepressant effects of bupropion. On the contrary, the &agr;5 nAChR subunit deletion did not alter the FST behavior in the bupropion‐treated mice. Not only in the transgenic mice, bupropion also showed antidepressant‐like effects in the WT mice. In addition, DH&bgr;E pretreatment before bupropion administration resulted in decreased immobility time and increased climbing time. Taken together, the present study provides evidence on the involvement of &agr;4*, &agr;6*, and &bgr;2* (* indicates possible presence of other subunits) nAChRs in the antidepressant‐like effects of bupropion in the FST.