Kefir protective effects against nicotine cessation-induced anxiety and cognition impairments in rats

Authors

1 Department of Food Hygiene, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background: Nicotine as one of the potent psychostimulant drugs is characterized by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine intake, a number of symptoms such as anxiety, depression and cognition impairment develop. Kefir as a food supplement is rich in tryptophan. In this study, we have evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression and cognition impairment.
Materials and Methods: Forty adult male rats were divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17 days and then the negative control groups got 5 mg/kg/day of normal saline. The positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5 mg/kg/day for 7 days. On the 25 th day, Elevated Plus Maze (EPM), Open Field Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and depression. In addition, Moris Water Maze was applied to evaluate learning and memory in the animals between the 20 th and 25 th days.
Results: The results showed that administration of CMK, SMK and Sertraline had higher anti-depression and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment results in the nicotine withdrawal period (P < 0.05).
Conclusion: This study revealed that Kefir had a potential effect on the treatment of nicotine cessation-induced depression, anxiety and cognition impairment in the animal model. Kefir may be useful for adjunct therapy for nicotine abandonment treatment protocols.

Keywords

1.
Mansvelder HD, McGehee DS. Cellular and synaptic mechanisms of nicotine addiction. J Neurobiol 2002;53:606-17.  Back to cited text no. 1
    
2.
Dani JA, Ji D, Zhou FM. Synaptic plasticity and nicotine addiction. Neuron 2001;31:349-52.  Back to cited text no. 2
    
3.
Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 2002;13:1097-106.  Back to cited text no. 3
    
4.
Kenny PJ, Markou A. Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity. Neuropsychopharmacology 2006;31:1203-11.  Back to cited text no. 4
    
5.
Staley JK, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl JP, et al. Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse 2001;41:275-84.  Back to cited text no. 5
    
6.
Rao TS, Correa LD, Adams P, Santori EM, Sacaan AI. Pharmacological characterization of dopamine, norepinephrine and serotonin release in the rat prefrontal cortex by neuronal nicotinic acetylcholine receptor agonists. Brain Res 2003;990:203-8.  Back to cited text no. 6
    
7.
Chae Y, Yeom M, Han JH, Park HJ, Hahm DH, Shim I, et al. Effect of acupuncture on anxiety-like behavior during nicotine withdrawal and relevant mechanisms. Neurosci Lett 2008;430:98-102.  Back to cited text no. 7
    
8.
Kenny PJ, Markou A. Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav 2001;70:531-49.  Back to cited text no. 8
    
9.
Benowitz NL. Neurobiology of nicotine addiction: Implications for smoking cessation treatment. Am J Med 2008;121(4 Suppl 1):S3-10.  Back to cited text no. 9
    
10.
George TP, O'Malley SS. Current pharmacological treatments for nicotine dependence. Trends Pharmacol Sci 2004;25:42-8.  Back to cited text no. 10
    
11.
Olausson P, Engel JA, Söderpalm B. Involvement of serotonin in nicotine dependence: Processes relevant to positive and negative regulation of drug intake. Pharmacol Biochem Behav 2002;71:757-71.  Back to cited text no. 11
    
12.
Sacco KA, Termine A, Seyal A, Dudas MM, Vessicchio JC, Krishnan-Sarin S, et al. Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: Involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry 2005;62:649-59.  Back to cited text no. 12
    
13.
Garrote GL, Abraham AG, De Antoni GL. Chemical and microbiological characterisation of kefir grains. J Dairy Res 2001;68:639-52.  Back to cited text no. 13
    
14.
Otles S, Cagindi Oe. Kefir: A probiotic dairy-composition, nutritional and therapeutic aspects. Pak J Nutr 2003;2:54-9.  Back to cited text no. 14
    
15.
Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses 2006;67:362-70.  Back to cited text no. 15
    
16.
Kubow S, Fotouhinia M. Kefir as a potent anti-oxidant composition. US Patent 20,040,028,696; 2004.  Back to cited text no. 16
    
17.
Singer S, Rossi S, Verzosa S, Hashim A, Lonow R, Cooper T, et al. Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function. Neurochem Res 2004;29:1779-92.  Back to cited text no. 17
    
18.
Cary DD. Nicotine addiction treatment. Google Patents; 2001.  Back to cited text no. 18
    
19.
Harrison AA, Liem YT, Markou A. Fluoxetine combined with a serotonin-1A receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats. Neuropsychopharmacology 2001;25:55-71.  Back to cited text no. 19
    
20.
Morissette SB, Tull MT, Gulliver SB, Kamholz BW, Zimering RT. Anxiety, anxiety disorders, tobacco use, and nicotine: A critical review of interrelationships. Psychol Bulletin 2007;133:245-72.  Back to cited text no. 20
    
21.
Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review. Eur J Pharmacol 2003;463:3-33.  Back to cited text no. 21
    
22.
Carobrez A, Bertoglio L. Ethological and temporal analyses of anxiety-like behavior: The elevated plus-maze model 20 years on. Neurosci Biobehav Rev 2005;29:1193-205.  Back to cited text no. 22
    
23.
Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol 2004;7:387-90.  Back to cited text no. 23
    
24.
D'Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 2001;36:60-90.  Back to cited text no. 24
    
25.
Tomkins DM, Sellers EM. Addiction and the brain: The role of neurotransmitters in the cause and treatment of drug dependence. CMAJ 2001;164:817-21.  Back to cited text no. 25
    
26.
Neumeister A. Tryptophan depletion, serotonin, and depression: Where do we stand? Psychopharmacol Bull 2002;37:99-115.  Back to cited text no. 26
    
27.
Lacasse JR, Leo J. Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS Med 2005;2:e392.  Back to cited text no. 27
    
28.
Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: A patient-level meta-analysis. JAMA 2010;303:47-53.  Back to cited text no. 28
    
29.
Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 2007;356:1711-22.  Back to cited text no. 29
    
30.
Alberghina D, Giannetto C, Visser EK, Ellis AD. Effect of diet on plasma tryptophan and serotonin in trained mares and geldings. Vet Rec 2010;166:133-6.  Back to cited text no. 30
    
31.
Meltzer HY, Horiguchi M, Massey BW. The role of serotonin in the NMDA receptor antagonist models of psychosis and cognitive impairment. Psychopharmacology (Berl) 2011;213:289-305.  Back to cited text no. 31
    
32.
Fukami H, Tachimoto H, Kishi M, Kaga T, Tanaka Y. Acetic acid bacterial lipids improve cognitive function in dementia model rats. J Agric Food Chem 2010;58:4084-9.  Back to cited text no. 32
    
33.
Holub I, Kozianowski G. Isomaltulose for use in enhancing mental performance. Google Patents; 2011.  Back to cited text no. 33
    
34.
Shaw KA, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002;1.  Back to cited text no. 34
    
35.
Rodrigues KL, Caputo LR, Carvalho JC, Evangelista J, Schneedorf JM. Antimicrobial and healing activity of kefir and kefiran extract. Int J Antimicrob Agents 2005;25:404-8.  Back to cited text no. 35
    
36.
Moreira ME, Dos Santos MH, Zolini GP, Wouters AT, Carvalho JC, Schneedorf JM. Anti-inflammatory and cicatrizing activities of a carbohydrate fraction isolated from sugary kefir. J Med Food 2008;11:356-61.  Back to cited text no. 36
    
37.
Doðan M. Rheological behaviour and physicochemical properties of kefir with honey. Journal für Verbraucherschutz und Lebensmittelsicherheit 2011;6:327-32.  Back to cited text no. 37
    
38.
Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 2002;71:533-54.  Back to cited text no. 38
    
39.
Hasselbalch SG, Madsen K, Svarer C, Pinborg LH, Holm S, Paulson OB, et al. Reduced 5-HT2A receptor binding in patients with mild cognitive impairment. Neurobiol Aging 2008;29:1830-8.  Back to cited text no. 39
    
40.
Harvey JA. Role of the serotonin 5-HT(2A) receptor in learning. Learn Mem 2003;10:355-62.  Back to cited text no. 40
    
41.
Haider S, Khaliq S, Haleem DJ. Enhanced serotonergic neurotransmission in the hippocampus following tryptophan administration improves learning acquisition and memory consolidation in rats. Pharmacol Rep 2007;59:53-7.  Back to cited text no. 41
    
42.
Brezun JM, Daszuta A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience 1999;89:999-1002.  Back to cited text no. 42
    
43.
Lauder JM, Krebs H. Serotonin as a differentiation signal in early neurogenesis. Dev Neurosci 1978;1:15-30.  Back to cited text no. 43
    
44.
Asemi Z, Jazayeri S, Najafi M, Samimi M, Mofid V, Shidfar F, et al. Effect of daily consumption of probiotic yogurt on oxidative stress in pregnant women: A randomized controlled clinical trial. Ann Nutr Metab 2012;60:62-8.  Back to cited text no. 44
    
45.
Ghoneum M, Gimzewski J. Apoptotic effect of a novel kefir product, PFT, on multidrug-resistant myeloid leukemia cells via a hole-piercing mechanism. Int J Oncol 2014;44:830-7.  Back to cited text no. 45