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

Piotr Popik*, Ewa Kozela, Martyna Krawczyk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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 mgkg -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-β-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-β-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.

Original languageAmerican English
Pages (from-to)1196-1202
Number of pages7
JournalBritish Journal of Pharmacology
Issue number6
StatePublished - Jul 2003
Externally publishedYes


  • Antidepressants
  • Citalopram
  • Depression
  • Dihydro-β-erythroidine
  • Imipramine
  • Mecamylamine
  • Mice
  • Nicotinic receptors
  • Tail-suspension test
  • nAChR


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