Evidence for the Involvement of Nmda Receptors in the Antidepressant-Like Effect of Nicotine in Mouse Forced Swimming and Tail Suspension Tests Publisher Pubmed



Hajmirzaian A^{1, 2} ; Kordjazy N^{1, 2} ; Hajmirzaian A^{1, 2} ; Ostadhadi S^{1, 2} ; Ghasemi M³ ; Amiri S^{1, 2} ; Faizi M⁴ ; Dehpour A^{1, 2}
Source: Psychopharmacology Published:2015

Abstract

Rationale: 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. Objectives: We attempted to evaluate the possible role of N-Methyl-d-aspartate (NMDA) receptors in the antidepressant-like effect of nicotine. Methods: 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. Results: 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. Conclusions: 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. © 2015 Springer-Verlag Berlin Heidelberg.