Nicotine and nicotinic receptor antagonists potentiate the antidepressant-like effects of imipramine and citalopram

1 Epidemiological and clinical observations suggest the involvement of nicotinic acetylcholine receptors (nAChRs) in depressive illness. Nonetheless, there is no clearcut evidence that nicotine and/or nAChR antagonists produce an antidepressant effect. 2 In the tail-suspension test (C57/Bl male mice), nicotine (0.8 - 1.2 mg kg(-1) s.c. or i.p.) given 15-60 min before the measurement exerted no effect on immobility. 3 Given 30 min before the measurement, citalopram (2 mg kg(-1)) produced a slight decrease in immobility; coadministration of nicotine (0.8 mg kg(-1), 15 but not 40 min before the test) to citalopram-treated mice resulted in a robust decrease in immobility. Imipramine (4 mg kg(-1)) did not affect immobility, but given in combination with 0.8 mg kg(-1) of nicotine (15 but not 40 min before the test), a decrease in immobility was observed. Nicotine (0.8 and 1.2 mg kg(-1)) also produced an enhancement in the anti-immobility effect of imipramine (20 mg kg(-1)). 4 We further investigated if nAChR antagonists would influence the antidepressant-like effects of imipramine and citalopram. Unexpectedly, mecamylamine (1 - 2.5 mg kg(-1)) and dihydro-beta-erythroidine ( 2 mg kg(-1)) potentiated the antidepressant-like effect of imipramine (4 - 20 mg kg(-1)). Mecamylamine ( 2.5 mg kg(-1)) but not dihydro-beta-erythroidine also increased the antidepressant-like effect produced by 2 mg kg(-1) of citalopram. 5 The interaction between nAChR antagonists and antidepressants appeared synergistic. 6 Neither nAChR ligands, antidepressants nor combinations of the two, affected locomotor activity. 7 The present results demonstrate an unexpected interaction between nAChR ligands and imipramine and citalopram in the tail-suspension test.