Show simple item record

dc.contributor.advisorSara, Mehmet Yıldırım
dc.contributor.authorTaş, Sadık Taşkın
dc.date.accessioned2018-05-21T08:42:44Z
dc.date.available2018-05-21T08:42:44Z
dc.date.issued2018
dc.date.submitted2018-01-18
dc.identifier.citationVancouver Citation Styletr_TR
dc.identifier.urihttp://hdl.handle.net/11655/4485
dc.description.abstractAntihistamines are one of the most widely used drug groups in various indications such as allergy, common cold and insomnia. Although these drugs are known to cause central nervous system side effects, their effects on cognitive functions such as learning and memory are not fully elucidated. We used in vivo hippocampal field potential recordings to assess the neuroplasticity changes caused by acute and chronic diphenhydramine and cetirizine treatment. Scopolamine is also used to assess the antimuscarinic effects of diphenhydramine. Furthermore, behavioral experiments were conducted to investigate the effect of cetirizine on cognitive performance. An REM sleep deprivation model was used to assess the effects of cetirizine in pathophysiological conditions. Acute use of diphenhydramine and cetirizine affected the potentiation phases of short-term plasticity while chronic treatment caused a tolerance to this effect. In long-term plasticity experiments, cetirizine blocked LTD in all groups and inhibited LTP in chronic treatment. Cetirizine prevented REM sleep deprivation-induced inhibition of LTP. Behavioral experiments with acute and chronic cetirizine treatment yielded no significant results. Our data showed that cetirizine has a significant effect in long-term plasticity that diphenhydramine failed to elicit. Therefore, cetirizine might be affecting the hippocampal circuitry independent of H1 receptor blockage through a previously unknown mechanism. Cetirizine use during sleep deprivation could be protective against cognitive dysfunction.en
dc.description.sponsorshipHacettepe Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi, Proje Numarası: THD-2017-16553tr_TR
dc.description.tableofcontentsAPPROVAL PAGE iii YAYIMLAMA VE FİKRİ MÜLKİYET HAKLARI BEYANI iii ETHICAL DECLARATION v ACKNOWLEDGEMENTS vi ÖZET vii ABSTRACT viii TABLE OF CONTENTS ix SYMBOLS AND ABBREVIATIONS xiii LIST OF FIGURES xv LIST OF TABLES xvii 1. INTRODUCTION 1 2. GENERAL INFORMATION 6 2.1. Histamine 6 2.1.1. Chemical Properties of Histamine 6 2.1.2. Synthesis of Histamine 7 2.2. Histamine Receptors 8 2.2.1. Histamine H1 Receptor 8 2.2.2. Histamine H2 Receptor 10 2.2.3. Histamine H3 Receptor 11 2.2.4. Histamine H4 Receptor 12 2.3. Role of Histamine in Homeostatic Brain Functions 12 2.4. Role of Histamine in Higher Brain Functions 15 2.5. Antihistamines 19 2.5.1. First Generation Antihistamines 20 2.5.2. Diphenhydramine 22 2.5.3. Second Generation Antihistamines 22 2.5.4. Cetirizine 23 2.6. Third Generation Antihistamines 24 2.7. Aim and Hypotheses 24 3. MATERIALS AND METHODS 26 3.1. Animals 26 3.2. Drugs 26 3.3. Protocols and Groups 27 3.3.1. Acute Treatment Electrophysiology Groups 27 3.3.2. Chronic Drug Electrophysiology Groups 28 3.3.3. Acute Cetirizine Behavioral Experiment Groups 28 3.3.4. Chronic Cetirizine Behavioral Experiment Groups 29 3.3.5. Acute Cetirizine REM Sleep Deprivation Groups 29 3.4. In Vivo Hippocampal Electrophysiology 31 3.4.1. Stratum Pyramidale Recordings 32 3.4.2. Stratum Radiatum Recordings 33 3.4.3. Long-Term Potentiation Recordings 33 3.4.4. Long-Term Depression Recordings 34 3.5. Behavioral Experiments 34 3.5.1. Open Field Arena 34 3.5.2. Elevated Plus Maze 34 3.5.3. Passive Avoidance 35 3.5.4. Forced Swim Test 35 3.5.5. Morris water maze 36 3.5.6. Morris water maze reversal learning 36 3.6. REM Sleep Deprivation 37 3.7. Analysis 37 4. RESULTS 38 4.1. Electrophysiology Experiments of Acute Treatment Groups 38 4.1.1. Input/Output Results from Strata Radiatum and Pyramidale of Acute Treatment Groups 38 4.1.2. Paired-Pulse Stimulation Results from Strata Radiatum and Pyramidale of Acute Treatment Groups 42 4.1.3. Long-Term Potentiation and Long-Term Depression Results of Acute Treatment Groups 44 4.2. Electrophysiology Experiments of Chronic Treatment Groups 46 4.2.1. Input/Output Results from Strata Radiatum and Pyramidale of Chronic Treatment Groups 46 4.2.2. Paired-Pulse Stimulation Results from Strata Radiatum and Pyramidale of Acute Treatment Groups 51 4.2.3. Long-Term Potentiation and Long-Term Depression Results of Chronic Treatment Groups 53 4.3. Behavioral Experiments of Acute Cetirizine Treatment Groups 55 4.3.1. Open Field Arena Results of Acute Cetirizine Treatment Groups 55 4.3.2. Elevated Plus Maze Results of Acute Cetirizine Treatment Groups 56 4.3.3. Passive Avoidance Results of Acute Cetirizine Treatment Groups 57 4.3.4. Forced Swim Test Results for Acute Cetirizine Treatment Groups 58 4.3.5. Morris Water Maze Results for Acute Cetirizine Treatment Groups 59 4.4. Behavioral Experiments of Chronic Cetirizine Treatment Groups 60 4.4.1. Open Field Arena Results of Chronic Cetirizine Treatment Group 60 4.4.2. Elevated Plus Maze Results of Chronic Cetirizine Treatment Group 61 4.4.3. Passive Avoidance Results of Chronic Cetirizine Treatment Group 62 4.4.4. Forced Swim Test Results for Chronic Cetirizine Treatment Group 63 4.4.5. Morris Water Maze Results for Chronic Cetirizine Treatment Group 64 4.4.6. Morris Water Maze Reversal Learning Results for the Chronic Treatment Group 65 4.5. Acute Cetirizine REM Deprivation Experiments 67 4.5.1. Input/Output Results from Strata Radiatum and Pyramidale of REM Sleep Deprivation Groups 67 4.5.2. Paired-Pulse Stimulation Results from Strata Radiatum and Pyramidale of REM Sleep Deprivation Groups 71 4.5.3. Long-Term Potentiation and Long-Term Depression Results of REM Sleep Deprivation Groups 73 5. DISCUSSION 75 5.1. Acute Cetirizine but Not Diphenhydramine Treatment Decreased Firing Threshold of CA1 Pyramidal Neurons 75 5.2. Acute Treatment with All Drugs Tested Decreased PP Facilitation in Both Strata Radiatum and Pyramidale 76 5.3. Acute Cetirizine Treatment Blocked LTD but Not LTP 77 5.4. Chronic Cetirizine and Diphenhydramine Treatment Did Not Alter the CA1 Synaptic Transmission Properties 78 5.5. Chronic Cetirizine and Scopolamine Treatment Inhibited Long-Term Plasticity 79 5.6. Behavioral Experiments with 5 Mg/Kg Cetirizine Did Not Elicit Any Significant Effects. 80 5.7. Cetirizine Improved Synaptic Transmission Disrupted by REMD in Stratum Radiatum but Not in Stratum Pyramidale 80 5.8. Cetirizine Prevented Inhibition of LTP by REM Sleep Deprivation 81 5.9. Conclusion 82 6. REFERENCES 83 7. APPENDICES Appendix 1: Hayvan Deneyleri Yerel Etik Kurulu Kararı 8. CURRICULUM VITÆtr_TR
dc.language.isoentr_TR
dc.publisherSağlık Bilimleri Enstitüsütr_TR
dc.rightsinfo:eu-repo/semantics/openAccesstr_TR
dc.subjectantihistaminik ilaçlartr_TR
dc.subjectöğrenmetr_TR
dc.subjectbellektr_TR
dc.subjectsetirizintr_TR
dc.subjectdifenhidramintr_TR
dc.subjectREM uyku yoksunluğutr_TR
dc.titleThe Effects of Acute and Chronic Diphenhydramine and Cetirizine Use on Learning and Memory in Ratstr_TR
dc.title.alternativeAkut ve Kronik Difenhidramin ve Setirizin İlaç Kullanımının Sıçanlarda Öğrenme ve Bellek Üzerine Etkileritr_TR
dc.typeinfo:eu-repo/semantics/doctoralThesisen
dc.description.ozetAntihistaminik ilaçlar alerji, nezle ve uykusuzluk gibi birçok endikasyonu olan ve çok yaygın olarak kullanılan bir ilaç grubudur. Bu ilaçların santral sinir sistemi yan etkileri yaptığı bilinmesine rağmen öğrenme ve bellek gibi bilişsel fonksiyonlar üzerine etkileri tam olarak aydınlatılamamıştır. Bu çalışmada in vivo hipokampal alan potansiyeli kayıtları kullanılarak akut ve kronik setirizin ve difenhidramin tedavisi ile gelişen nöroplastisite değişikliği etkileri incelendi. Difenhidraminin antimuskarinik etkilerini değerlendirmek için ise skopolamin kullanıldı. Ayrıca, setirizinin kognitif performans üzerinde etkilerini araştırmak için davranış deneyleri yapıldı. Setirizinin patofizyolojik koşullardaki etkilerini araştırmak için de bir REM uyku yoksunluğu modeli kullanıldı. Difenhidramin ve setirizin akut kullanımı kısa dönem plastisitenin potansiyasyon fazlarını engelledi ancak kronik kullanımda bu etkiye tolerans gelişti. Uzun dönem plastisite deneylerinde setirizin tüm gruplarda LTD’yi ve kronik tedavi grubunda LTP’yi inhibe etti. Akut ve kronik setirizin tedavisi sonrası yapılan davranış deneylerinde anlamlı bir sonuç alınamadı. Bu sonuçlar setirizinin uzun dönem plastisite üzerine difenhidraminin oluşturamadığı etkileri olduğunu göstermektedir. Bu bulgulara göre, setirizin hipokampal devreleri H1 reseptör blokajı dışında daha önce bilinmeyen bir mekanizma ile etkiliyor olabilir. Uyku yoksunluğu sırasında setirizin kullanımı kognitif bozukluklara karşı koruyucu olabilir.tr_TR
dc.contributor.departmentTıbbi Farmakolojitr_TR


Files in this item

This item appears in the following Collection(s)

Show simple item record