Role of nicotine in depression through dopaminergic mechanism


  • Rahul Raghunath Bhalsinge Department of Pharmacology, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
  • Rajbhoj Satkar Department of Pharmacology, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
  • Sayan Das Department of Pharmacology, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
  • Shraddha Yadav Department of Pharmacology, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
  • Shah A. S. Department of Pharmacology, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
  • P. S. Worlikar Department of Pharmacology, Dr. D.Y. Patil Medical College, Pimpri, Pune, Maharashtra, India



Catalepsy, Dopamine, Depression, Haloperidol induced catalepsy, Isolation induced hyperactivity, Nicotine


Background: There are interesting reports in the literature indicating relationship of smoking /nicotine and depression. Smokers use nicotine to treat depression. The objectives of present study were to evaluate the role of nicotine in depression through Dopaminergic mechanism by using haloperidol induced catalepsy model in rats and to estimate Dopamine level in brain of depressed rats after nicotine and imipramine.

Methods: Dopaminergic activity was evaluated in haloperidol induced catalepsy in rats. Levels of dopamine in normal as well as in depressed rats brain was estimated using fluorimetric method. The study treatment were administered as follows - Vehicle (s.c.), Imipramine (i.p.) - 7days, Nicotine (subcutaneous), Nicotine (inhalation) were administered in a dose of 1ml/kg,10mg/kg,0.4mg/kg,0.2mg/kg respectively.

Results: In haloperidol induced catalepsy model, vehicle treated group showed cataleptic effect starting at 1 hour and lasting for 6 hours. Nicotine administered by subcutaneous route significantly reduced cataleptic score as compared to vehicle treated group till 6 hours. Nicotine administered by inhalation route reduced cataleptic score up to 6 hours compared with that of vehicle. Catalepsy score in nicotine (inhalation) group was significantly less as compared to nicotine (subcutaneous) at all time points period except 2 hours. Isolation induced hyperactivity model was used to induce depression in rats. Dopamine levels in rats after isolation were significantly less as compared to normal rats (before isolation). After isolation, dopamine levels in imipramine treated rats were significantly higher as compared to vehicle treated group. After isolation, dopamine levels were significantly high in both groups i.e., nicotine (subcutaneous) and nicotine (inhalation). Imipramine (7 days) and single dose of nicotine (inhalation) showed comparable results with normal dopamine level i.e. before isolation rats.

Conclusions: Nicotine has increased dopaminergic activity as evident by reversal of haloperidol induced catalepsy. Dopamine level reduced in depressed rats. Dopamine brain levels were increased, when depressed rats were treated with Imipramine (i.p.), nicotine (s.c.), nicotine(inhaled). Single dose nicotine given by inhalation route has produced significant antidepressant action comparable to that of seven days’ treatment of standard antidepressant drug imipramine in rats. In rats, nicotine by both routes i.e subcutaneous and inhalational increased dopaminergic activity.


Barroso MG. Depression: Clinical definition and case histories. The International J Transpersonal Studies. 2003;22:89-99.

Markou A, Thomas RK, George FK. Neurobiological similarities in depression. Neuropsychopharmacology. 1998;18(3):135-74.

Baldessarini RJ. Drug therapy of depression and anxiety disorders. In Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 11th Ed. New York: McGraw-Hill, Medical Publishing Division. 2006:429-59.

Debattista C. Antidepressant agents. In.Chapter 30. Katzung BG, Masters SB, Trevor AJ. Basic and clinical Pharmacology. 11th Ed. McGraw-Hill, Medical Publishing Division. 2009:509-30.

Khisti RT, Mandhane SN, Chopde CT. Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease. Indian Exp Biol. 1997;35(12):1297-301.

Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007;64:327-37.

Mathur R. Antidepressants. In: Drug Screening Methods, Gupta, S.K. (Ed.). Chapter 8. Jaypee Brothers, New Delhi, India, ISBN-13: 978-8180613975; 2004:76-82.

Green AR, Bloomfield MR, Attwewill CK, Costain DW. Electroconvulsive shock reduces the cataleptogenic effect of both haloperidol and arecoline in rats. Neuropharmacology. 1979;18:447-51.

Rao KV. Biostatistics- A manual of statistical methods for use in health, nutrition and anthropology. Jaypee Brothers, 2nd Ed. 2007:226-60.

Abdel-salam OM, Baiuomy AR. Effect of different drugs influencing monoamine neurotransmission on haloperidol-induced catalepsy in mice. Turk J Med Sci. 2007;37(6):333-8.

Abin-Carriquiry JA, Urbanavicius J, Scorza C, Rebolledo-Fuentes M, Wonnacott S, Cassels BK. Increase in locomotor activity after acute administration of the nicotinic receptor agonist 3-bromocytisine in rats. Eur J Pharmacol. 2010;634:89-94.

Popik P, Krawczyk M, Koz T, Nalepa I. Nicotine produces antidepressant like actions: behavioral and neurochemical evidence. Eur J Pharmacol. 2005;515:128-33.

Potdar VH, Kibile SJ. Evaluation of antidepressant-like effect of citrus maxima leaves in animal models of depression. Iran J Basic Med Sci. 2011;14(5):478-83.

Skolnick P. Antidepressants for the new millennium. Eur J Pharmacol. 1999;375(1-3):31-40.

Semba J, Matake C, Yamada S, Nankai M, Toru M. Antidepressant like effects of chronic nicotine on learned helplessness paradigm in rats. Bio Psychiatry. 1998;43(5):389-91.




How to Cite

Bhalsinge, R. R., Satkar, R., Das, S., Yadav, S., S., S. A., & Worlikar, P. S. (2017). Role of nicotine in depression through dopaminergic mechanism. International Journal of Basic & Clinical Pharmacology, 6(4), 864–867.



Original Research Articles