Antidepressant-like action of nicotine in forced swimming test and brain serotonin in mice

Article · July 2006with10 Reads
DOI: 10.1016/j.physbeh.2006.05.007 · Source: PubMed
Abstract
An antidepressant-like action of nicotine has been suggested in the forced swimming test. The aim of the present study was to evaluate the relationship between the antidepressant-like action of nicotine and brain serotonin (5-HT) in mice. Nicotine at a dose of 0.2 mg/kg significantly (p < 0.05) decreased the duration of immobility time in forced swimming test. However, nicotine (0.01-1 mg/kg, s.c.) had no effect on locomotor activity in open-field test. Dopamine turnover in mouse whole brain was increased by nicotine (0.01-1 mg/kg, s.c.) in a dose-dependent manner, and nicotine at a dose of 0.05 mg/kg showed a significant increases in 5-HT turnover. Nicotine at a dose of 0.05 mg/kg markedly enhanced head twitch responses induced by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2A/2C receptor agonist. These findings suggest that the involvement of nicotinic and serotonergic systems in the antidepressant-like effects of nicotine.
  • ... In vivo pharmacokinetic studies were conducted in mice with 35 administered intravenously as a bolus dose (2 mg/kg), with further details provided in the supporting information. The compound was rapidly cleared (Cl ¼ 117 mL/min$kg), had a short half-life (t 1/ Despite the far from ideal pharmacokinetic properties of 35, compounds with short half-lives are still able to display activity through the forced-swim test (FST) as a result of the short duration of the procedure (6 min) [28,29]. While the pharmacokinetic profile of 35 would make it unsuitable for clinical development, and is by no means a viable lead candidate itself, we believe it is sufficient for proof-of-concept studies in the FST. ...
  • ... Furthermore, in some daily smokers, direct anxiogenic and depressogenic effects, which disappear following smoking cessation, have been reported [8][9][10], and the involvement of the combined activation and desensitization of nicotinic acetylcholine receptors (nAChRs) was suggested in the direct causal link between smoking and emotional symptoms using several rodent experimental models [11, 12]. On the other hand, NC-induced anxiolytic and antidepressant effects have also been reported depending on the experimental model, the route of NC administration and the time course of administration [3,[13][14][15][16][17], and these effects are thought to characteristically reinforce the habitual use of NC. Anxiety and depression are also observed as frequent psychiatric outcomes of various stressors in humans and associated with inappropriate regulation of brain stress systems [18, 19]. ...
  • ... Moreover, transdermal nicotine patches exert an antidepressant-like effect in non-smokers [14]. Animal model studies corroborate these effects of nicotine: An acute administration of nicotine elicits an antidepressive-like behavior [15] while long-term nicotine withdrawal promotes increased depressive-like behavior in adult mice [16,17]. Over the past two decades numerous studies have indicated that smoking is highly correlated with the development of depression [18,19] and recent studies indicate that both the offspring of women who smoke and adolescent smokers are more susceptible to depression in later life [20,21], whereas those who initiate smoking later in life are not [20]. ...
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