Effects of Restraint Stress and Nitric Oxide Synthase Inhibition on Learning and Strategy Preference in Young Adult Male Rats

Abstract

Objective: The aim of this study was to investigate the effects of restraint stress and nitric oxide synthase (NOS) inhibition by NωNitro-L-Arginine (LNA) on learning and strategy preference. Material and Methods: Rats were randomly divided into four groups (Saline, Saline+Stress, LNA, LNA+Stress). Stress was applied for one hour in glass cylinders during 13 days. One hour after this stress application, water maze experiments were started. Injections (saline 1 ml/kg or 50 mg/kg LNA) were given 10 minutes before each experiment. The platform was kept visible or hidden (on the 4th, 8th, 12th days) at the same position. On the 13th day the platform was located on the opposite quadrant. Results: Saline groups exhibited significantly better performances (F(1.31)=174.038 p<0.05) at the beginning compared to the NOS inhibited groups. For initial hidden platform days; stress was determined as an impairment factor (F(1.31)=5.190 p=0.012). At the end, acquisition occurred on both visible and hidden platform days for all groups. There was no significant strategy preference difference between the groups.Development of the stress and NOS inhibition impairments were seen, particularly at different periods of the acquisition. Conclusion: NOS inhibition did not worsen restraint stress-induced learning impairments in rats. Lack of effect may be explained by the antidepressive consequences of NOS inhibition. Turkish Başlık: Kısıtlama stresi ve nitrik oksit sentaz inhibisyonunun genç erişkin erkek sıçanlarda öğrenme ve strateji tercihi üzerine etkileri Anahtar Kelimeler: Diabetes mellitus, cynodon dactylon, elektromanyetik alan, insülin, glukoz Amaç: Prospektif, randomize ve çilf kör çalışmada septorinoplasti (SRP) ve endoskopik sinus cerrahisi (ESC) ameliyatlarından sonra levobupivakain ve tramadol infiltrasyonunun postoperatif analjezik etkilerinin araştırılması amaçlandı. Gereç ve Yöntemler: Çalışmaya elektif olarak ESC ve SRP operasyonları gerirecek ASA I-III sınıfı altmış erişkin hasta alındı. Anestezi indüksiyonu intravenöz propofol 2-2.5 mg/kg-1, roküronyum bromid 0.6 mg/kg-1, and fentanil 1 μg/kg-1 ile gerçekleştirildi. İdame %2 sevofluran ile N2O/O2 karışımı (FiO2: 35%) ile sağlandı. Operasyondan 10 dakika önce cerrahi sahaya tramadol 0.5 mg/kg-1(Group T: n= 20), levobupivakain %0.25(Group L: n= 20), ve lidokainin %1(Group C: n= 20) adrenaline solüsyonu 1/200000 infiltre edildi (ESC için 5 mL ve SRP için10 mL). Postoperatif dönemde hastaların tümüne hasta kontrollü analjezi cihazı ile fentanil uygulandı (bolus doz: 15 μg ve kilit aralığı:10 dak). Ağrı postoperative ilk 24 saatte 11 dereceli vizüel analog skala (VAS) ile 4 saat ara ile değerlendirildi. Postoperatif dönemde analjezik gereksinim, opioid tüketimi ve yan etkiler belirlenerek kaydedildi. Bulgular: Tramadol verilen grubun fentanil gereksinim ve tüketimi istatistiksel açıdan farklı bulundu. 24 saatlik fentanyl dozları Grup C, L ve T için sırası ile 345.2 ± 168.8,6 μg, 221.1 ± 120.6 μg; and 184.1 ± 130,3 μg (p= 0.002) olarak belirlendi. Tramadol ve kontrol grubunun fentanil gereksinimlerinde 16, 20 ve 24. saat peryotlarda (p= 0.012, p= 0.004. ve p= 0.002) farklılık saptandı. Yan etki profili benzerdi. Sonuç: Bulgularımız ESC ve SRP operasyonlarından önce preemptif tramadol infiltrasyonunun levobupivakainin etkili, pratik ve güvenli bir alternatifi olduğunu düşündürmektedir.

Keywords

• Learning, NOS inhibition, restraint stress, strategy preference, water maze

Effects of Restraint Stress and Nitric Oxide Synthase Inhibition on Learning and Strategy Preference in Young Adult Male Rats

Öz

Kaynakça

1. Kumar RS, Narayanan SN, Nayak S. Ascorbic acid protects against restraint stress-induced memory deficits in wistar rats. Clinics (Sao Paulo) 2009;64:1211-7. [CrossRef]
2. Kanit L, Taskiran D, Furedy JJ, Kulali B, McDonald R, Pogun S. Nicotine interacts with sex in affecting rat choice between “look- out” and “navigational” cognitive styles in the Morris water maze place learning task. Brain Res Bull 1998;46:441-5. [CrossRef]
3. Domek-Lopacinska KU, Strosznajder JB. Cyclic GMP and nitric oxide synthase in aging and Alzheimer’s disease. Mol Neurobiol 2010;41:129-37. [CrossRef]
4. Hawkins RD, Son H, Arancio O. Nitric oxide as a retrograde mes- senger during long-term potentiation in hippocampus. Prog Brain Res 1998;118:155-72. [CrossRef]
5. Paakkari I, Lindsberg P. Nitric oxide in the central nervous system. Ann Med 1995;27:369-77. [CrossRef]
6. Ingram DK, Spangler EL, Meyer RC, London ED. Learning in a 14-unit T-maze is impaired in rats following systemic treatment with N omega-nitro-L-arginine. Eur J Pharmacol 1998;341:1-9. [CrossRef]
7. Lambert LE, Whitten JP, Baron BM, Cheng HC, Doherty NS, Mc- Donald IA. Nitric oxide synthesis in the CNS endothelium and macrophages differs in its sensitivity to inhibition by arginine ana- logues. Life Sci 1991;48:69-75. [CrossRef]
8. Echeverry MB, Guimaraes FS, Del Bel EA. Acute and delayed re- straint stress-induced changes in nitric oxide producing neurons in limbic regions. Neuroscience 2004;125:981-93. [CrossRef]

9. Sevgi S, Ozek M, Eroglu L. L-NAME prevents anxiety-like and de- pression-like behavior in rats exposed to restraint stress. Meth- ods. Find Exp Clin Pharmacol 2006;28:95-9. [CrossRef]
10. Ulak G, Mutlu O, Akar FY, Komsuoglu FI, Tanyeri P, Erden BF. Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats. Pharmacol Biochem Behav 2008;90:563-8. [CrossRef]
11. McDonald RJ, White NM. Parallel information processing in the water maze: evidence for independent memory systems involving dorsal striatum and hippocampus. Behav Neurol Biol 1994;61:260-70. [CrossRef]
12. Kitraki E, Kremmyda O, Youlatos D, Alexis MN, Kittas C. Gender- dependent alterations in corticosteroid receptor status and spa- tial performance following 21 days of restraint stress. Neurosci- ence 2004;125:47-55. [CrossRef]
13. Li XH, Liu NB, Zhang MH, Zhou YL, Liao JW, Liu XQ, et al. Ef- fects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats. Chin Med J (Engl) 2007;120:669-74.
14. Venero C, Tilling T, Hermans-Borgmeyer I, Schmidt R, Schachner M, Sandi C. Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1. Neuroscience 2002;115:1211-9. [CrossRef]
15. Conrad CD. A critical review of chronic stress effects on spatial learning and memory. Prog Neuropsychopharmacol Biol Psychia- try 2010;34:742-55. [CrossRef]
16. Hara H, Waeber C, Huang PL, Fuiji M, Fishman MC, Moskow- itz MA. Brain distribution of nitric oxide synthase in neuronal or endothelial nitric oxide synthase mutant mice using [3H]L-NG- nitro-arginine autoradiography. Neuroscience 1996;75:881-90. [CrossRef]
17. O’Dell TJ, Huang PL, Dawson TM, Dinerman JL, Snyder SH, Kan- del ER, et al. Endothelial NOS and the blockade of LTP by NOS inhibitiors in mice lacking neuronal NOS. Science 1994;265:542-6. [CrossRef]
18. Holscher C, McGlinchey L, Anwyl R, Rowan MJ. 7-nitro indazole, a selective neuronal nitric oxide synthase inhibitor in vivo, impairs spatial learning in the rat. Learn Mem 1996;2:267-78. [CrossRef]
19. Sandi C, Venero C, Guaza C. Decreased spontaneous motor ac- tivity and startle response in nitric oxide synthase inhibitor-treat- ed rats. Eur J Pharmacol 1995;227:89-97. [CrossRef]
20. Kanit L, Koylu E, Yararbas G, Furedy JJ, Pogun S. The effect of nitric oxide synthase inhibition on cognitive ability and strategies employed for place learning in the water maze: sex differences. Brain Res Bull 2003;62:151-9. [CrossRef]
21. Mogensen J, Wortwein G, Hasman A, Nielsen P, Wang Q. Func- tional and neurochemical profile of place learning after L-nitro-ar- ginine in the rat. Neurbiol Learn Mem 1995;63:54-65. [CrossRef]
22. Koylu EO, Kanit L, Taskiran D, Dagci T, Balkan B, Pogun S. Effects of nitric oxide synthase inhibition on spatial discrimination learn- ing and central DA2 and mACh receptors. Pharmacol Biochem Behav 2005;81:32-40. [CrossRef]
23. Maljessi N, Kadkhodaee M, Parviz M, Nagdhi N. Serotonin de- pletion in rat hippocampus attenuates L-NAME-induced spatial learning deficits. Brain Res 2003;963:244- 51. [CrossRef]
24. Echeverry MB, Guimaraes FS, Oliveira MA, do Prado WA, Del Bel EA. Delayed stress-induced antinociceptive effect of nitric oxide synthase inhibition in the dentate gyrus of rats. Pharmacol Bio- chem Behav 2002;74:149-56. [CrossRef]
25. Harkin A, Connor TJ, Burns MP, Kelly JP. Nitric oxide synthase inhibitors augment the effects of serotonin re-uptake inhibi- tors in the forced swimming test. Eur Neuropsychopharmacol 2004;14:274-81. [CrossRef]
26. Wultsch T, Chourbaji S, Fritzen S, Kittel S, Grunblatt E, Gerlach M, et al. Behavioral and expressional phenotyping of nitric oxide syn- thase-I knockdown animals. J Neural Transm Suppl 2007;72:69-85. [CrossRef]
27. Sung JY, Goo JS, Lee DE, Jin DQ, Bizon JL, Gallagher M, et al. Learning strategy selection in the water maze and hippocampal CREB phosphorylation differ in two inbred strains of mice. Learn Mem 2008;15:183-8. [CrossRef]