Antidepressant-like action of nicotine in forced swimming test and brain serotonin in mice
Division of Pharmacy, Ehime University Hospital, Shitsukawa Toon, Ehime, 791-0295, Japan. Physiology & Behavior
(Impact Factor: 2.98).
07/2006; 88(4-5):545-9. DOI: 10.1016/j.physbeh.2006.05.007
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.
Available from: Arya Haj-Mirzaian
- "We studied the effect of four different doses of nicotine (0.03, 0.1, 0.2, and 0.5 mg/kg) on FST and TST comparing to the immobility time of the control group, which had been given 5 ml/kg physiological saline (Suemaru et al. 2006). Also, nicotine 0.2 mg/kg was administered 15, 30, and 60 min before the behavioral tests to obtain the best time of action for our following experiments (Suemaru et al. 2006; Tizabi et al. 1999). "
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ABSTRACT: The antidepressant action of acute nicotine administration in clinical and animal studies is well recognized. But the underlying mechanism for this effect has not been carefully discovered.
We attempted to evaluate the possible role of N-Methyl-D-aspartate (NMDA) receptors in the antidepressant-like effect of nicotine.
After the assessment of locomotor activity in the open-field test, forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of nicotine in mice. We performed intraperitoneal administration of nicotine at different doses and periods before the tests. To assess the possible involvement of NMDA receptors, non-effective doses of NMDA antagonists and an NMDA agonist were obtained and were administered simultaneously with the non-effective and effective doses of nicotine, respectively.
Nicotine (0.2 mg/kg, 30 min before FST/TST) significantly reduced the immobility time of mice similar to fluoxetine (20 mg/kg). Nicotine did not affect the locomotor behavior of mice in open-field test. Co-administration of non-effective doses of NMDA receptor antagonists, ketamine (1 or 0.3 mg/kg), MK-801 (0.05 or 0.005 mg/kg), and magnesium sulfate (10 or 5 mg/kg) with nicotine (0.1 or 0.03 mg/kg) had remarkable synergistic antidepressant effect in both FST and TST. Also, non-effective NMDA (75 or 30 mg/kg) reversed the anti-immobility effect of nicotine (0.2 mg/kg) on mouse FST and TST.
Our study has for the first time confirmed that the antidepressant-like effect of nicotine on mice is NMDA-mediated, and nicotine presumably exerts this effect by antagonizing the glutamatergic NMDA receptors.
Available from: Katarzyna Targowska-Duda
- "Mice were treated with subcutaneous (s.c.) injections of 0.57 mg/kg nicotine tartrate prepared in saline solution (0.9% NaCl) at a volume of 10 ml/kg. This dose corresponds to 0.2 mg/kg nicotine base, which has been shown to produce antidepressant-like effects (Suemaru et al., 2006). Since PAM-2 is not water soluble, ethanol:PEG200:water (10:20:70, by vol.) was used as vehicle, as previously indicated (Targowska-Duda et al., 2014). "
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ABSTRACT: The current study compares the antidepressant-like effect elicited by nicotine between wild-type (β4+/+) and knockout (β4-/-) mice, and subsequently, the effect of 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a positive allosteric modulator of α7 nicotinic receptors, on the previously determined activity of nicotine. Mice from each sex were injected daily with nicotine base (0.2 mg/kg; s.c.) or co-administered with PAM-2 (1.0 mg/kg; i.p.) for three weeks. Forced swim tests were performed to determine the acute (Day 1), subchronic (Day 7), and chronic (Days 14 and 21) effects of the drugs, as well as their residual effects after treatment cessation (Days 28 and 35). Our results indicate that nicotine mediates antidepressant-like activity after acute, subchronic, and chronic treatments in β4+/+, but not β4-/-, mice, and that these effects are not mediated by unspecific locomotor stimulation. Nicotine co-administered with PAM-2 produces antidepressant-like activity in both β4+/+ and β4-/- mice, except after the acute treatment of β4-/- mice, and decreases locomotor activity. This suggests that although the β4 subunit regulates the antidepressant-like activity of nicotine it does not affect the activity elicited by PAM-2 when is co-administered with nicotine. The residual antidepressant-like activity of PAM-2+nicotine was observed only in female mice, suggesting gender-specific differences. Our findings clearly indicate that β4-containing nAChRs play an important role in the antidepressant-like activity elicited by nicotine but they are not essential for the modulatory activity of PAM-2. In fact, PAM-2 inhibits α4β4 and α3β4 AChRs at higher concentration ranges compared to that for the PAM activity previously found at the α7 AChR.
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Available from: Eduardo Weruaga
- "Thus, constant and continuous nicotine administration seems to act as a potent anxiolytic in NOS1−/− males. This is in accordance with previous results indicating a modulatory role of nicotine on the serotonergic system, hence influencing anxiety-related behavior (Benwell and Balfour 1982a, b; File et al. 2000; Seth et al. 2002; Suemaru et al. 2006). Taken together, our data support the idea of a modulatory action of NO in anxiety-related neurophysiological responses (López-Figueroa et al. 1998; Weruaga et al. 2002). "
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ABSTRACT: Nitric oxide (NO) is a messenger synthesized in both the neuronal and glial populations by nitric oxide synthase type 1 (NOS1). Nicotine regulates NO production in a sex-dependent manner, both molecules being involved in motor function.
The present study evaluates sex differences in motor coordination, general movement, and anxiety-related responses resulting from both constant and continuous nicotine treatment and the genetic depletion of NOS1 activity.
Male and female mice were analyzed with the open-field and the rotarod tests. To understand the role of NO, knockout mice for NOS1 (NOS1-/-) were analyzed. Nicotine was administered continuously at a dose of 24 mg/kg/day via osmotic mini-pumps over 14 days because the behavioral effects elicited are similar to those observed with discontinuous administration.
Data analyses revealed noteworthy sex differences derived from NOS1 depletion. Control NOS1-/- males exhibited an exacerbated anxiety-related response in relation to control NOS1-/- females and control wild-type (WT) males; these differences disappeared in the nicotine-administered NOS1-/- males. Additionally, nicotine administration differentially affected the horizontal movements of NOS1-/- females with respect to WT animals. NO depletion affected male but not female motor coordination improvement along the test days. However, the drug affected female motor coordination only at the end of the administration period.
We show for the first time that NO affects motor and anxiety behaviors in a sex-dependent manner. Moreover, the behavioral effects of constant nicotine administration are dimorphic and dependent on NO production.
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