title: Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests.
abstract: Current literature suggests that nicotinic acetylcholine receptors (nAChRs) are involved in major depression. In rodents, antidepressant-like effects of both nicotine and the non-selective nAChR antagonist mecamylamine have been reported. Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Thus, we hypothesise that nicotine may enhance the behavioural effects of serotonin (e.g., citalopram) and/or noradrenaline (e.g., reboxetine) reuptake inhibitors. Here, we tested if nicotine enhanced the activity of citalopram or reboxetine in the mouse forced swim test (mFST) and the mouse tail suspension test (mTST). The potential for mecamylamine to augment antidepressant drug action was also investigated. Sub-threshold and threshold doses of citalopram (3 and 10mg/kg) or reboxetine (3, 10 and 20mg/kg) were tested alone and in combination with nicotine (0.3 and 1.0mg/kg) and mecamylamine (1 and 3mg/kg). Locomotor activity experiments were performed to rule out non-specific stimulant effects. Nicotine (1.0mg/kg) enhanced the effect of 10mg/kg citalopram and 20mg/kg reboxetine in the mFST. Similarly, nicotine (1.0mg/kg) enhanced the effect of 3 and 10mg/kg citalopram and 3 and 10mg/kg reboxetine in the mTST. No concomitant locomotor stimulation was observed at the tested dose combinations. Mecamylamine was effective on its own in some tests, but did not augment the effects of citalopram or reboxetine at the doses tested. The data show that nicotine enhances the effects of both serotonin and noradrenaline reuptake inhibitors, possibly reflecting nicotine's facilitating effects on the release of these two neurotransmitters, and indicating that nicotine may enhance antidepressant action.
authors.affiliation: Department of Affective Disorders, Neurosearch A/S, 93 Pederstrupvej, DK-2750 Ballerup, Denmark.
authors.forename: Jesper T
authors.initials: JT
authors.lastname: Andreasen
authors.forename: John P
authors.initials: JP
authors.lastname: Redrobe
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D000077593:Reboxetine; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D015283:Citalopram; D008464:Mecamylamine; D009025:Morpholines; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009638:Norepinephrine; D000077593:Reboxetine; D011978:Receptors, Nicotinic; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors