Oksibutininin Farelerde Pasif Sakınma ve Morris Su Tankı Testlerinde Öğrenme Ve Bellek İşlevleri Üzerine Etkileri

Yıl 2022, Cilt: 12 Sayı: 1, 98 - 106, 18.03.2022

Mehmet Hanifi Tanyeri Mehmet Emin Büyükokuroğlu Pelin Tanyeri Aykut Öztürk Rümeysa Keleş Şeyma Nur Başarır Bozkurt Oguz Mutlu

https://doi.org/10.31832/smj.1021067

Öz

Amaç: Aşırı aktif mesane (AAM) çocukluk çağı inkontinans nedenlerinin çoğunluğunu oluşturmaktadır. Oksibutinin, AAM tedavisinde çocuklarda sıklıkla kullanılan antimuskarinik bir maddedir. Çalışmamızın amacı antimuskarinik ilaçlardan biri olan oksibutininin öğrenme ve bellek üzerine etkilerinin araştırılmasıdır.
Gereç ve Yöntemler: Farelerde Pasif Sakınma (PA) Testi ve Morris Su Tankı (MWM) Testini kullanarak oksibutinin’in öğrenme ve hafıza üzerindeki etkilerini değerlendirdik.
Bulgular: Oksibutinin tedavisinin (1 mg/kg, 2 mg/kg ve 4 mg/kg) kontrole göre ikinci gün tutma süresinde önemli bir farklılık göstermermezken, skopolamin uygulanmış farelerde oksibutinin (4 mg/kg) retansiyon süresini önemli ölçüde uzatmıştır. MWM Testinde, oksibutinin (1 mg/kg, 2 mg/kg ve 4 mg/kg) hedef kadranda geçirilen süre üzerinde hiçbir etkisi yoktur. Skopolamin (0,6 mg/kg) tek başına hedef kadranda harcanan süreyi önemli ölçüde azalttı, ancak oksibutinin (4 mg/kg), skopolamin ile tedavi edilen farelerde hedef kadranda geçirilen süreyi önemli ölçüde uzattı. Ayrıca, skopolamin, kaçış platformuna olan ortalama mesafeyi önemli ölçüde artırırken, oksibutinin (4 mg/kg), skopolamin ile tedavi edilen farelerde kaçış platformuna olan ortalama mesafeyi önemli ölçüde azalttı.
Sonuç: Çalışmamızda oksibutinin öğrenme ve belleği etkilemezken, bozulmuş öğrenme ve bellek üzerine olumlu etkileri olduğu görülmüştür. Bu çalışmanın sonuçları AAM'li hastalarda oksibutinin kullanımının öğrenme ve hafızayı etkilemediğini göstermektedir.

Anahtar Kelimeler

oksibutinin, skopolamin, öğrenme, bellek, fare

The Effects of Oxybutynin on Learning and Memory Functions In Passive Avoidance and Morris Water Maze Tests In Mice

Öz

Objective: Overactive bladder (OAB) constitutes the majority of childhood incontinence causes. Oxybutynin is an antimuscarinic agent frequently used for children in the treatment of OAB. This study aimed to investigate the effects of an antimuscarinic drug oxybutynin on learning and memory.
Materials and Methods: We assessed the effects of oxybutynin on learning and memory functions using the Passive Avoidance (PA) and the Morris Water Maze (MWM) Test in mice.
Results: Oxybutynin treatment (1 mg/kg, 2 mg/kg, and 4 mg/kg) did not show a significant difference in the retention time on the second day compared to the control and oxybutynin (4 mg/kg) significantly prolonged the retention time in scopolamine-treated mice. In the MWM Test, oxybutynin (1 mg/kg, 2 mg/kg, and 4 mg/kg) has no effect on the time spent in the target quadrant. Scopolamine (0.6 mg/kg) alone significantly reduced time spent in the target quadrant, but oxybutynin (4 mg/kg) significantly prolonged time spent in the target quadrant in scopolamine-treated mice. Also, scopolamine significantly increased the mean distance to the escape platform, while oxybutynin (4 mg/kg) significantly decreased the mean distance to the escape platform in scopolamine-treated mice.
Conclusion: In our study, oxybutynin did not affect learning and memory, but it plays a role ameliorating the learning and memory deficits. The results of this study show that the use of oxybutynin in patients with OAB does not affect learning and memory.

Anahtar Kelimeler

oxybutynin, scopolamine, learning, memory, mice

Kaynakça

• 1- Jacek Tomaszewski. Postmenopausal overactive bladder. Prz Menopauzalny 2014;13(6):313-329.
• 2- Corsos J, Przydacz M, Campeau L, Witten J, Hickling D, Honeine C, et. al. CUA Guideline On Adult Overactive Bladder 2017;11(5): E142–E173.
• 3- Lam S and Hilas O. Pharmacologic management of overactive bladder. Clinical Interventions in Aging 2007;2(3) 337–345.
• 4-Yoshimura N and Chancellor MB. Current and future pharmacological treatment for overactive bladder. J Urol. 2002;168:1897–1913.
• 5-Product Information, 2004a. Ditropan XL®, oxybutynin chloride extendedrelease tablets. Ortho-McNeil Pharmaceutical, Inc., New Jersey, USA.
• 6-Staskin DR, MacDiarmid SA. Pharmacologic management of overactive bladder: practical options for the primary care physician. Am J Med 2006;119:24S–8S.
• 7- Zobrist RH, Schmid B, Feick A. Pharmacokinetics of the Rand S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers. Pharm Res 2001;18:1029–1034.
• 8-Abramowicz M, et al. Detrol LA and Ditropan XL for overactive bladder. Med Letter 2001;43:28–29.
• 9-Abramowicz M, et al. Oxybutynin transdermal (Oxytrol) for overactive bladder. Med Letter 2003;45:38–39.
• 10-Mutlu O, Akar F, Celikyurt I, Tanyeri P, Ulak G, Erden F. 7-NI and ODQ Disturbs Memory in the Elevated plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice. Drug Target Insights 2015;9:1–8.
• 11- Sawada H, Oeda T, Yamamoto K, Umemura A, Tomita S, Hayashi R et. al. Trigger medications and patient-related risk factors for Parkinson disease psychosis requiring anti-psychotic drugs: a retrospective cohort study. BMC Neurology 2013;13:145.
• 12-Ulak G, Mutlu O, Tanyeri P, Komsuoglu FI, Akar F, Erden F. Involvement of serotonin receptor subtypes in the antidepressant-like effect of trim in the rat forced swimming test. Pharmacology Biochemistry & Behavior 2010;95:308-314.
• 13- Maj J, Rogóz Z, Skuza G, Sowińska H. The effect of antidepressant drugs on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist. Neuropharmacology. 1992;31(7):685-691.
• 14- Madhuvrata P, Cody JD, Ellis G, Herbison GP, Hay-Smith EJ, et al. Which anticholinergic drug for overactive bladder symptoms in adults. Cochrane Database Syst Rev 2012;1:CD005429.
• 15- Robinson D, Cardozo L, Milsom I, Pons ME, Kirby M, Koelbl H, et. al. Oestrogens and overactive bladder. Neurourol Urodyn 2014;33:1086-1091.
• 16- Robinson D, Toozs-Hobson P and Cardozo L. The effect of hormones on the lower urinary tract. Menopause Int 2013;19:155-162.
• 17- Oefelein MG. Safety and tolerability profiles of the anticholinergic agents used for the treatment of overactive bladder. Drug Saf 2011;34:733-754.
• 18- Vorhees CV & Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc2006;1:848–858.
• 19- Tanyeri P, Buyukokuroglu ME, Mutlu O, Ulak G, Akar FY, Celikyurt IK, et. al. Effects of ziprasidone, SCH23390 and SB277011 on spatialmemory in the Morris water maze test in naive and MK-801 treated mice. Pharmacol Biochem Behav 2015;138:142–147.
• 20- Zain MA, Rouhollahi E, Pandy V, Mani V, Majeed AA, Wong WF, et. al. Phencyclidine dose optimisation for induction of spatial learning and memory deficits related to schizophrenia in C57BL/6 mice. Exp Anim 2018;67:421–429.
• 21- Nigam A, Kulshreshtha M, Panjwani D. Pharmacological evaluation of Hibiscus abelmoschus against scopolamine-induced amnesia and cognitive impairment in mice. Adv Hum Biol 2019;9:116-123.