DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20171108

Effect of nicotine on serotonin (5-HT) levels in brain of depressed rats

Rahul R. Bhalsinge, Anita A. Barde, Pratibha S. Worlikar, Manasi V. Limaye, Mrunal P. Dhole, Abhijeet V. Tilak

Abstract


Background: Reduction in brain serotonin (5-HT) levels contributes to depression. Nicotine may have antidepressant properties and smokers self-medicate underlying depression. Epidemiological findings suggest that smokers more often demonstrate depressive symptoms than non-smokers and depressed patients are less likely to cease smoking. Therefore, the study was planned to evaluate the effect of nicotine on serotonin levels in brain of depressed rats.

Methods: Antidepressant action of study drugs was evaluated using isolation induced hyperactivity model in rats. Rats were divided into five groups with six rats in each group. Study groups: Vehicle in normal rats 1 ml/kg (subcutaneous); vehicle after isolation 1ml/kg (subcutaneous); imipramine 10 mg/kg (intraperitoneal) for 7 consecutive days; single dose of nicotine 0.4 mg/kg (subcutaneous); single dose of nicotine 0.2 mg/kg (inhalational). Brain serotonin assay was carried out. The statistical significance was determined by ANOVA followed by Tukey test (p<0.05).

Results: Serotonin levels (55.93ng/g of brain tissue) in rats after isolation were significantly less than in normal rats (335.87ng/g) (p<0.001). In imipramine treated group, serotonin levels (301.4ng/g) after isolation were highly significant as compared to serotonin levels in vehicle treated group after isolation (p<0.001). Nicotine administered by subcutaneous and inhalational route showed significantly higher brain serotonin levels, i.e. 175ng/g and 254.62ng/g respectively as compared to vehicle treated rats after isolation (p<0.001).

Conclusions: Single dose nicotine (inhalational) 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 serotonergic activity.


Keywords


Depression, Isolation induced hyperactivity model, Nicotine, Serotonin

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References


Reus VI. Mental Disorders. In: Psychiatric disorders. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine. 17th ed. New York. McGraw-Hill, Medical Publishing Division; 2008.

Shirayama Y, Chaki S. Neurochemistry of the nucleus accumbens and its relevance to depression and antidepressant action in rodents. Curr Neuropharmacol. 2006;4(4):277-91.

Rafael J, Pascual S. Nicotine antidepressant effects as a predictor of response to desipramine or fluoxetine in non-smoking major depressed patients. Salud Ment. 2002;25(02):16-20.

Popik P, Krawczyk M, Kos T, Nalep I. Nicotine produces andidepressant-like actions: Behavioural and neurochemical evidence. Eur J Pharmacol. 2005;51:128-33.

Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport. 2002;13(9):1097-106.

Turner Jr, Castellano LM, Blendy JA. Nicotinic partial agonists varenicline and sazetidine-a have differential effects on affective behavior. J Pharmacol Exp Ther. 2010;334(2):665-72.

Baldessarini RJ. Drugs and treatment of psychiatric disorders. In: Hardman JG, Limbird LE, Gilman AG. editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 10th ed. New York. McGraw-Hill, Medical Publishing Division; 2001.

Harmer CJ, Goodwin GM, Cowen PJ. Why do antidepressants take so long to work? a cognitive neuropsychological model of antidepressant drug action. Br J Psychiatry. 2009;195(2):102-8.

Rohan KJ, Lindsey KT, Roecklein KA, Lacy TJ. Cognitive-behavioural therapy, light therapy and their combination in treating seasonal affective disorder. J Affect Disord. 2004;80(2-3):273-83.

Tamboli AM, Rub RA, Ghosh P, Bodhankar SL. Antiepileptic activity of lobeline isolated from the leaf of Lobelia nicotianaefolia and its effect on brain GABA level in mice. Asian Pac J Trop Biomed. 2012;2(7):537-42.

Chiplonkar SA, Rao KV. In: Analysis of Variance. KV Rao, editor. Biostatistics: A manual of statistical methods for use in health, nutrition and anthropology. 2nd ed. New Delhi. Jaypee Brothers Medical Publishers (P) Ltd; 2007.

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

Skolnick P, Legutko B, Li X, Bymaster FP. Current perspectives on the development of non-biogenic amine-based antidepressants. Pharmacol Res. 2001;43(5):411-23.

Markou A, Kosten TR, Koob GF. Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacol. 1998;18(3):135-74.

Salín-Pascual RJ, Drucker-Colín R. A novel effect of nicotine on mood and sleep in major depression. Neuroreport. 1998;9(1):57-60.

Salin-Pascual RJ, de la Fuente JR, Galicia-Polo L, Drucker-Colin R. Effect of transdermal nicotine on mood and sleep in nonsmoking major depressed patients. Psychopharmacol (Berl). 1995;121(4):476-9.

Parrott AC. Cigarette derived nicotine is not a medicine. World J Biol Psychiatry. 2003;4:49-55.

Leon LA, Cardenas FP. Contribution of the dopaminergic system to the effect of chronic fluoxetine in the rat forced swim test. Psychol Neurosci. 2008;1(1):81-6.

Mitchell PJ, Redfern PH. Animal models of depressive illness: The importance of chronic drug treatment. Curr Pharm Des. 2005;11:171-203.

Turner JR, Castellana LM, Blendy JA. Nicotinic partial agonists varenicline and sazetidine-A have differential effects on affective behaviour. J Pharmacol Exp Ther. 2010;334(2):665-72.

Mineur YS, Eibl C, Young G, Kochevar C, Papke RL, Gündisch D, Picciotto MR. Cytisine-based nicotine partial agonists as novel antidepressant compounds. J Pharmacol Exp Ther. 2009;329(1):377-86.