RESEARCH PAPER
Prolonged exposure to transdermal nicotine improves memory in male mice, but impairs biochemical parameters in male and female mice
 
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1
Chair and Department of Hygiene Medical University of Lublin, Poland
2
Students’ Scientific Association at the Chair and Department of Hygiene, Medical University, Lublin, Poland
 
KEYWORDS:
TOPICS:
ABSTRACT:
Introduction:
Nicotine is an alkaloid that affects the functioning of the central nervous system and produces dependence. In low doses, it acts as a stimulant and relaxant. Nicotine was reported to have pro-cognitive effects in humans and animals. However, high doses of nicotine are harmful for many organs.The aim of the study was to check whether a 30-day exposure to transdermal nicotine affects memory and biochemical parameters in mice.

Material and methods:
A total of 32 mice (16 males and 16 females) were used in the experiment. Mice were divided into 4 groups of 8 animals each: I control-females receiving placebo patches for 30 days, II females receiving nicotine patches for 30 days, III control-males receiving placebo patches, IV males receiving nicotine patches. Spontaneous alternation and locomotor activity were examined weekly in a Y-maze. Body mass was recorded daily. On day 30, venous blood samples were obtained and the animals were anaesthetized with CO2. Their blood was used to measure alanine transaminase (ALT), asparagine transaminase (AST), cholesterol, creatinine and glycosylated haemoglobin (HbA1C).

Results:
Nicotine significantly improved memory in male mice on day 8. It increased ALT and AST activities in males and females, as well as the concentration of cholesterol in their blood sera.

Conclusions:
In conclusion, transdermal nicotine may produce transient improvement in fresh spatial memory in male mice, but it is not a long-term effect and therefore nicotine does not seem to be appropriate for use in the treatment of neurodegenerative disorders. It elevates blood cholesterol level and thus may increase the risk of atherosclerosis and cardiovascular events; moreover, it negatively affects liver enzymes. Nicotine use is therefore not recommended.

CORRESPONDING AUTHOR:
Barbara Nieradko-Iwanicka   
Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
 
REFERENCES (39):
1. Benowitz NL, Hukkanen J, Jacob P,III. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol 2009; 92: 29–60.
2. Harrington L, Viñals X, Herrera-Solís A, Flores A,Morel C, Tolu S, et al. Role of β4* nicotinic acetylcholine receptors in the habenulo-interpeduncular pathway in nicotine reinforcement in mice. Neuropsychopharmacology. 2015 Nov 20. doi: 10.1038/npp.2015.346. [Epub ahead of print]. cited 23.11.2015.
3. Subramaniyan M, Dani JA. Dopaminergic and cholinergic learning mechanisms in nicotine addiction. Ann N Y Acad Sci. 2015; 1349(1): 46–63.
4. Ezzati M, Riboli E. Behavioral and dietary risk factors for noncommunicable diseases. N Engl J Med. 2013; 369 (10): 954–64.
5. Leone A, Landini L Jr, Biadi O, Balbarini A. Smoking and cardiovascular system: cellular features of the damage. Curr Pharm Des. 2008; 14(18): 1771–7.
6. Feng JH, Yan YE, Liang G, Liu YS, Li XJ, Zhang BJ, Chen LB, Yu H, He XH, Wang H. Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation. Mol Cell Endocrinol. 2014; 394(1–2): 59–69.
7. Sanner T, Grimsrud TK. Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review. Front Oncol. 2015; 5: 196| doi: 10.3389/fonc.2015.00196.
8. Bassett RA, Osterhoudt K, Brabazon T. Nicotine Poisoning in an Infant N Engl J Med. 2014; 370: 2249–50.
9. Raunio H, Pokela N, Puhakainen K, Rahnasto M, Mauriala T, Auriola S, Jovonen RO. Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo. Xenobiotica 2008; 38 (1): 34–47.
10. Szymańska JA, Frydrych B, Bruchajzer E. Nikotyna dokumentacja dopuszczalnych wielkości narażenia zawodowego. Podstawy i Metody Oceny Środowiska Pracy 2007; 2 (52): 121–154.
11. Yingst JM, Veldheer S, Hrabovsky S, Sciamanna C, Foulds J. Reasons for non-adherence to nicotine patch therapy during the first month of a quit attempt. Int J Clin Pract. 2015; 69(8): 883–8.
12. Gould TJ, Prescott PT. Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning. Neurobiol Learn Mem. 2014; 107: 108–32.
13. Larsson A, Engel JA. Neurochemical and behavioral studies on ethanol and nicotine interactions. Neurosci Biobehav Rev. 2004; 27(8): 713–20.
14. Zaniewska M, Mc Creary AC, Wydra K, Faron-Gorecka A, Filip M. Context-controlled nicotine-induced changes in the labeling of serotonin (5-HT) 2A and 5-HT 2C receptors in the rat brain. Pharm Rep 2015; 67: 451–459.
15. Klaassen CD, Watkins III JB. Casarett &Doull’s Essentials of Toxicology. 2 nd ed. New York: McGraw-Hill2010 [chapter 22].
16. Swan GE, Lessov-Schlaggar CN. The effects of tobacco smoke and nicotine on cognition and the brain. Neuropsychol Rev. 2007; 17(3): 259–73.
17. Leibovici D, Ritchie K, Ledesert B, Touchon J. The effects of wine and tobacco consumption on cognitive performance in the elderly: a longitudinal study of relative risk. Int J Epidemiol. 1999; 28(1): 77–81.
18. Sarter M, Bodewitz G, Stephens DN. Attenuation of scopolamine-induced impairment of spontaneous alternation behavior by antagonist but not inverse agonist and agonist β-carbolines. Psychopharmacology 1988; 94: 491–5.
19. Klaassen CD, Watkins III JB. Casarett &Doull’s Essentials of Toxicology. 2 nd ed. New York: McGraw-Hill 2010 [chapter 3].
20. Hukkanen J, Jacob P, III, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005; 57: 79–115.
21. Niemegeers P, Dumont GJ, Quisenaerts C, Morrens M, Boonzaier J, Fransen E, et al. The effects of nicotine on cognition are dependent on baseline performance. Eur Neuropsychopharmacol. 2014; 24(7): 1015–23.
22. Seidl R, Tiefenthaler M, Hauser E, Lubec G. Effects of transdermal nicotine on cognitive performance in Down’s syndrome. Lancet 2000; 356 (9239): 1409–10.
23. AhnAllen CG, Bidwell LC, Tidey JW. Cognitive effects of very low nicotine content cigarettes, with and without nicotine replacement, in smokers with schizophrenia and controls. Nicotine Tob Res. 2015; 17(5): 510–4.
24. Wing V, Sacco K, George T. Spatial working memory impairments induced by cigarette smoking abstinence are correlated with plasma nicotine levels in schizophrenia. Schizophrenia Res. 2011; 128 (1–3): 171–2.
25. Gupta T, Mittal VA. Nicotine usage is associated with elevated processing speed, spatial working memory, and visual learning performance in youth at ultrahigh-risk for psychosis. Psychiatry Res. 2014; 220(1–2): 687–90.
26. Newhouse PA, Potter A, Singh A. Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol. 2004; 4(1): 36–46.
27. Noshita T, Murayama N, Murayama S. Effect of nicotine on neuronal dysfunction induced by intracerebroventricular infusion of amyloid-β peptide in rats. Eur Rev Med Pharmacol Sci. 2015; 19(2): 334–43.
28. Li P, Beck WD, Callahan PM, Terry AV, Bartletta MG. Pharmacokinetics of cotinine in rats: A potential therapeutic agent for disorders of cognitive function. Pharm Rep. 2015; 76(3): 494–500.
29. Evans DE, Jentink KG, Sutton SK, Van Rensburg KJ, Drobes DJ. 7 mg nicotine patch fails to enhance P300 neural indices of cognitive control among nonsmokers. Pharmacol Biochem Behav. 2014; 126: 77–82.
30. Robinson D, Whitehead P. Effect of body mass and other factors on serum liver enzyme levels in men attending for well population screening. Ann Clin Biochem. 1989; 26: 393–400.
31. Fahim MA, Nemmar A, Al-Salam S, Dhanasekaran S, Shafiullah M, Yasin J, Hassan MY. Thromboembolic injury and systemic toxicity induced by nicotine in mice. Gen Physiol Biophys. 2014; 33(3): 345–55.
32. Goodman and Gilman’s the pharmacological basis of therapeutics. Hardman J G Ed. 9. ed. New York, Mc Graw-Hill, 1996:192.
33. Hua P, Feng W, Ji S, Raij L, EA. Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers. Am J Physiol Renal Physiol. 2010; 299(4): 732–39.
34. Ashakumary L, Vijayammal PL. Effect of nicotine on lipoprotein metabolism in rats. Lipids. 1997; 32(3): 311–315.
35. Warwas M, Żurawska-Płaksej E, Ciężka D, Piwowar A. Glycated albumin as a marker of glycemia in diabetes and its vascular complications; Postepy Hig Med Dosw. 2015; 69: 638–48. [Article in Polish].
36. McCulloch P, Lee S, Higgins R, McCall K, Schade DS. Effect of smoking on hemoglobin A1c and body mass index in patients with type 2 diabetes mellitus. J Investig Med. 2002; 50(4): 284–7.
37. Clair C, Bitton A, Meigs JB, Rigotti NA. Relationships of cotinine and self-reported cigarette smoking with hemoglobin A1c in the U.S.: results from the National Health and Nutrition Examination Survey, 1999–2008. Diabetes Care 2011; 34(10): 2250–5.
38. Elahy M, Lam V, Pallebage-Gamarallage MM, Giles C, Mamo JC, Takechi R. Nicotine attenuates disruption of blood-brain barrier induced by saturated-fat feeding in wild-type mice. Nicotine Tob Res. 2015; 17(12): 1436–41.
39. Kaleta D, Fronczak A. Disparities in exposure to tobacco smoke pollution at Romanian worksites. Ann Agric Environ Med. 2015; 22(4): 755–761.
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