Sam Sze Wing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 156-184). / Abstracts in English and Chinese. / Publications based on work in this thesis --- p.ii / Abstract --- p.iii / Acknowledgements --- p.vii / Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Corticosteroids --- p.2 / Chapter 1.1.1 --- Chemical Structure of Steroids --- p.3 / Chapter 1.1.2 --- Biosynthesis of Endogenous Corticosteroids --- p.3 / Chapter 1.1.2.1 --- Regulation of Cortisol synthesis and negative feedback system --- p.4 / Chapter 1.1.3 --- Biological Significance of Corticosteroids --- p.5 / Chapter 1.1.3.1 --- Involvement of corticosteroids as anti-inflammatory drugs --- p.6 / Chapter 1.1.3.2 --- Eicosanoid biosynthesis --- p.7 / Chapter 1.1.3.3 --- Lipoxygenase pathway --- p.9 / Chapter 1.1.3.4 --- Side-effects of prolonged use of corticosteroids --- p.9 / Chapter 1.2 --- Organisation of the Emetic Reflex --- p.11 / Chapter 1.2.1 --- Motor Pathway of Emetic Reflex --- p.12 / Chapter 1.2.1.1 --- Retching and vomiting --- p.12 / Chapter 1.2.1.2 --- Nausea --- p.13 / Chapter 1.2.2 --- Components of the Emetic Reflex --- p.14 / Chapter 1.2.2.1 --- The vomiting centre (VC) --- p.15 / Chapter 1.2.2.2 --- Area postrema (AP) / Chemoreceptor trigger zone (CTZ) --- p.15 / Chapter 1.2.2.3 --- The nucleus tractus solitarius (NTS) --- p.17 / Chapter 1.2.2.4 --- Gastrointestinal tract and vagus nerves --- p.17 / Chapter 1.2.2.5 --- Neurotransmitter receptors --- p.18 / Chapter 1.3 --- Chemotherapy-Induced Emesis --- p.19 / Chapter 1.3.1 --- Cancer as a cause of mortality in Man --- p.20 / Chapter 1.3.2 --- Chemotherapeutic Agents --- p.20 / Chapter 1.3.2.1 --- Different classes --- p.20 / Chapter 1.3.2.2 --- Emetogenic potential --- p.21 / Chapter 1.3.3 --- Cisplatin-Induced Emesis --- p.23 / Chapter 1.3.3.1 --- Unfavourable effects associated with chemotherapy-induced nausea and emesis --- p.24 / Chapter 1.3.3.2 --- Anticipatory nausea and vomiting --- p.24 / Chapter 1.3.3.3 --- Profile of cisplatin-induced emesis --- p.25 / Chapter 1.3.4 --- Animal Models of Cisplatin-Induced Acute and Delayed Emesis --- p.26 / Chapter 1.3.5 --- Mechanisms and Pathways Involves in Chemotherapy-Induced Emesis --- p.28 / Chapter 1.3.6 --- Anti-Emetic Drugs for the Treatment of Chemotherapy-Induced Emesis --- p.31 / Chapter 1.3.6.1 --- 5-HT3 receptor antagonists --- p.31 / Chapter 1.3.6.2 --- Dopamine receptor antagonists --- p.33 / Chapter 1.3.6.3 --- Benzodiazepines --- p.35 / Chapter 1.3.6.4 --- Cannabinoids --- p.35 / Chapter 1.3.6.5 --- Antihistamines and anticholinergics --- p.35 / Chapter 1.3.6.6 --- NK1 receptor antagonists --- p.37 / Chapter 1.3.6.7 --- Corticosteroids --- p.38 / Chapter 1.3.6.8 --- Multi-agent anti-emetic regimens --- p.39 / Chapter 1.4 --- Motion-Induced Emesis --- p.41 / Chapter 1.4.1 --- Incidence --- p.42 / Chapter 1.4.2 --- Mechanisms and Pathways Involved in Motion Sickness --- p.43 / Chapter 1.4.2.1 --- Importance of the vestibular apparatus --- p.44 / Chapter 1.4.2.2 --- Importance of the area postrema --- p.45 / Chapter 1.4.2.3 --- The nucleus tractus solitarius --- p.46 / Chapter 1.4.2.4 --- Hormone and neurotransmitters --- p.46 / Chapter 1.4.3 --- Animal models in Motion-Induced Emesis --- p.47 / Chapter 1.4.4 --- Anti-Emetic Drugs for the Treatment of Motion Sickness --- p.48 / Chapter 1.4.4.1 --- Anticholinergics --- p.49 / Chapter 1.4.4.2 --- Antihistamines --- p.49 / Chapter 1.4.4.3 --- Non-selective muscarinic and histamine receptor antagonists --- p.51 / Chapter 1.4.4.4 --- Sympathomimetics --- p.51 / Chapter 1.4.4.5 --- NK1i receptor antagonists --- p.51 / Chapter 1.4.4.6 --- 5-HT1A agonists --- p.52 / Chapter 1.4.4.7 --- 5-HT2 receptor agonist --- p.52 / Chapter 1.4.4.8 --- Arginine vasopressin (AVP) antagonists --- p.53 / Chapter 1.4.4.9 --- Opioid receptor agonists --- p.53 / Chapter 1.4.4.10 --- Dexamethasone and hormone levels --- p.54 / Chapter 1.4.4.11 --- Other anti-emetic drugs --- p.55 / Chapter 1.5 --- Aims of the Studies --- p.56 / Chapter 2 --- Methods --- p.59 / Chapter 2.1 --- Cisplatin-Induced Emesis Studies --- p.60 / Chapter 2.1.1 --- Animals --- p.60 / Chapter 2.1.2 --- Induction and Measurement of Emesis --- p.60 / Chapter 2.1.3 --- The Effects of Corticosteroids on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.63 / Chapter 2.1.4 --- "The Effects of Dexamethasone (1 mg/kg, i.p.) Administered as an Intervention Treatment on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.63 / Chapter 2.1.5 --- The Effects of Cortrosyn Depot (Tetracosactrin) on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.63 / Chapter 2.1.6 --- The Effects of Metyrapone on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.64 / Chapter 2.1.7 --- The Effects of Indomethacin on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.64 / Chapter 2.1.8 --- "The Effects of DFU and L-745,337 Administered as an Intervention Treatments on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.64 / Chapter 2.1.9 --- "The Effects of MK-886 (L-663,536) on Cisplatin-Induced Acute and Delayed Retching and Vomiting" --- p.65 / Chapter 2.1.10 --- The Effects of a Combination of Indomethacin and MK-886 on Cisplatin- Induced Acute and Delayed Retching and Vomiting --- p.65 / Chapter 2.1.11 --- Statistical Analysis --- p.66 / Chapter 2.2 --- Motion-Induced Emesis Studies --- p.67 / Chapter 2.2.1 --- Animals --- p.67 / Chapter 2.2.2 --- Measurement of Emesis --- p.67 / Chapter 2.2.3 --- Induction of Emesis in Motion-Naive Suncus murinus: Effects of Glucocorticoids --- p.68 / Chapter 2.2.4 --- Induction of Emesis in Motion-Sensitive Suncus murinus: Effects of Dexamethasone --- p.70 / Chapter 2.2.5 --- Preparation of Serum --- p.72 / Chapter 2.2.6 --- Measurement of Serum Cortisol by Enzyme-Linked Immunoassay (ELISA) --- p.72 / Chapter 2.2.6.1 --- Immunoassay kit --- p.72 / Chapter 2.2.6.2 --- Assay procedures --- p.73 / Chapter 2.2.7 --- Measurement of Serum Adrenocorticotrophin (ACTH) by Radioimmunoassay (RIA) --- p.75 / Chapter 2.2.7.1 --- Immunoassay kit --- p.75 / Chapter 2.2.7.2 --- Assay procedures --- p.76 / Chapter 2.2.8 --- Statistical Analysis --- p.79 / Chapter 3 --- Results --- p.81 / Chapter 3.1 --- Cisplatin-Induced Emesis --- p.82 / Chapter 3.1.1 --- General Profile of Emesis Induced by Cisplatin --- p.82 / Chapter 3.1.2 --- Antagonism of Cisplatin-Induced Emesis by Corticosteroids --- p.82 / Chapter 3.1.3 --- "The Effect of Dexamethasone (1 mg/kg, i.p.) Administered as an Intervention Treatment on an Established Delayed Retching and Vomiting Response Induced by Cisplatin" --- p.84 / Chapter 3.1.4 --- The Effect of Cortrosyn Depot (Tetracosactrin) on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.85 / Chapter 3.1.5 --- The Effect of Metyrapone on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.85 / Chapter 3.1.6 --- "The Effect of Indomethacin, DFU and L-745,337 on Cisplatin-Induced Acute and Delayed Retching and Vomiting" --- p.86 / Chapter 3.1.7 --- The Effect of MK-886 on Cisplatin-Induced Acute and Delayed Retching and Vomiting --- p.88 / Chapter 3.1.8 --- The Effect of Combination of Indomethacin and MK-886 on Cisplatin- Induced Acute and Delayed Retching and Vomiting --- p.89 / Chapter 3.2 --- Motion-Induced Emesis --- p.91 / Chapter 3.2.1 --- General Effect of Motion on Serum Cortisol and ACTH Levelsin Motion Naive Suncus murinus --- p.91 / Chapter 3.2.2 --- The Effect of Glucocorticoids on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion-Naive Male Suncus murinus --- p.92 / Chapter 3.2.2.1 --- Effect of dexamethasone --- p.92 / Chapter 3.2.2.2 --- Effect of betamethasone --- p.93 / Chapter 3.2.2.3 --- Effect of methylprednisolone --- p.93 / Chapter 3.2.3 --- The Effect of Glucocorticoids on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion Naive Female Suncus murinus --- p.94 / Chapter 3.2.3.1 --- Effect of dexamethasone --- p.94 / Chapter 3.2.3.2 --- Effect of betamethasone --- p.95 / Chapter 3.2.3.3 --- Effect of methylprednisolone --- p.95 / Chapter 3.2.4 --- The Effect of Dexamethasone on Motion-Induced Emesis and Cortisol and ACTH Levels in Motion-Sensitive Suncus murinus --- p.96 / Chapter 3.2.4.1 --- Effect of dexamethasone on male motion-sensitive animals --- p.97 / Chapter 3.2.4.2 --- Effect of dexamethasone on female motion-sensitive animals --- p.97 / Chapter 4 --- Discussion --- p.131 / Chapter 4.1 --- "Cisplatin (5 mg/kg, i.p.)-Induced Emesis in Control Animals" --- p.132 / Chapter 4.2 --- Anti-Emetic Action of Corticosteroids in the Ferret --- p.133 / Chapter 4.3 --- Metyrapone Study --- p.138 / Chapter 4.4 --- Cortrosyn Depot Study --- p.139 / Chapter 4.5 --- Role of Cycloxygenase --- p.141 / Chapter 4.6 --- Role of 5-Lipoxygenase --- p.143 / Chapter 4.7 --- Duel Inhibition of Cycloxygenase and 5-Lipoxygenase --- p.144 / Chapter 4.8 --- Anti-Emetic Potential of Glucocorticoids in Suncus murinus --- p.145 / Chapter 4.9 --- General Summary --- p.149 / Appendix I --- p.152 / Appendix II --- p.154 / References --- p.156

Wan Pui Chu Christina. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 167-191). / Abstracts in English and Chinese. / PUBLICATIONS BASED ON WORK IN THIS THESIS --- p.i / ABSTRACT --- p.ii / ACKNOWLEDGEMENT --- p.vii / TABLE OF CONTENTS --- p.viii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Introduction to the Vanilloid Receptor --- p.1 / Chapter 1.1.1 --- Properties of the VR1 Channel --- p.2 / Chapter 1.1.2 --- Explaining the Unexplained: De sensitization and Pungency --- p.6 / Chapter 1.2 --- The Quest for the Endogenous Ligand: Activation versus Modulation --- p.2 / Chapter 1.2.1 --- Anandamide and the Cannabinoid System --- p.12 / Chapter 1.2.2 --- Inflammatory Mediators and Lipid Metabolites --- p.15 / Chapter 1.3 --- The Variegated Vanilloid Receptor: Multiple Actions of TRPV1 --- p.18 / Chapter 1.3.1 --- Vanilloid-induced Hypothermia: some like it cold --- p.18 / Chapter 1.3.2 --- "Three's a crowd: Vanilloids, Substance P, and the Emetic Reflex" --- p.22 / Chapter 1.3.3 --- Grooming Behavior and Locomotor Changes: Further Involvement of Neurokinins? --- p.29 / Chapter 1.4 --- Aims and Objectives of the Present Study --- p.33 / Chapter CHAPTER 2 --- METHODS --- p.39 / Chapter 2.1 --- Animals --- p.39 / Chapter 2.2 --- Stereotaxic Surgery and Transmitter Implantation --- p.39 / Chapter 2.3 --- Measurement of Emesis and Genital Grooming --- p.41 / Chapter 2.4 --- Measurement of Locomotor Activity and Body Temperature --- p.41 / Chapter 2.5 --- Experimental Procedures for Central Injection Studies --- p.45 / Chapter 2.6 --- Experimental Procedures for Peripheral Injection Studies --- p.47 / Chapter 2.7 --- Drug Formulation --- p.48 / Chapter 2.8 --- Statistical Analysis --- p.49 / Chapter CHAPTER 3 --- RESULTS --- p.51 / Chapter 3.1 --- Actions of Intracerebroventricularly Administered Vanilloid Agonists --- p.51 / Chapter 3.1.1 --- General Behaviour --- p.51 / Chapter 3.1.2 --- Emetic Action of Vanilloids --- p.52 / Chapter 3.1.3 --- Anti-Emetic action of Vanilloids against Copper Sulphate --- p.55 / Chapter 3.1.4 --- Vanilloid-induced Hypothermia --- p.58 / Chapter 3.1.5 --- RTX-induced Genital Grooming --- p.65 / Chapter 3.1.6 --- Effects of Vanilloids on Locomotor Activity --- p.67 / Chapter 3.1.7 --- Summary of Central Agonist Studies --- p.76 / Chapter 3.2 --- Effects of Intracerebroventricularly Administered Capsazepine on Vanilloid-induced Responses --- p.78 / Chapter 3.2.1 --- Effect of Capsazepine on Vanilloid-induced Emesis --- p.78 / Chapter 3.2.2 --- Effect of Capsazepine on the Anti-Emetic Action of Vanilloids --- p.82 / Chapter 3.2.3 --- Effect of Capsazepine on Vanilloid-induced Hypothermia --- p.84 / Chapter 3.2.4 --- Effect of Capsazepine on RTX-induced Genital Grooming --- p.88 / Chapter 3.2.5 --- Effect of Capsazepine on Locomotor Activity of Vanilloid-treated Animals --- p.90 / Chapter 3.3 --- "Peripheral Studies with RTX，,Capsazepine, and Ruthenium Red" --- p.93 / Chapter 3.1.1 --- Experiment 1: Actions of Resiniferatoxin --- p.93 / Chapter 3.1.2 --- Experiment 2: Effects of Capsazepine and Ruthenium Red administered alone --- p.99 / Chapter 3.1.3 --- Experiment 3: Effects of Capsazepine and Ruthenium Red on RTX- induced Responses --- p.104 / Chapter CHAPTER 4 --- DISCUSSION --- p.113 / Chapter 4.1 --- General Considerations --- p.113 / Chapter 4.2 --- Emetic Action of Vanilloids --- p.116 / Chapter 4.3 --- Anti-Emetic Action of Vanilloids --- p.124 / Chapter 4.4 --- Hypothermic Action of Vanilloids --- p.133 / Chapter 4.5 --- Resiniferatoxin-induced Genital Grooming --- p.147 / Chapter 4.6 --- Actions of Capsazepine and Ruthenium Red --- p.152 / Chapter 4.7 --- Locomotor Activity --- p.157 / Chapter CHAPTER 5 --- SUMMARY --- p.162 / REFERENCES --- p.167

Capsaicin (1.3 mumol/kg, i.v.) and resiniferatoxin (48 nmol/kg, i.v.) failed to induce plasma extravasation in Suncus murinus (P>0.05). But SP (20 nmol/kg, i.v.) was able to induce salivation, and plasma extravasation in the bladder and the trachea significantly (P<0.05). NK1 receptor antagonists CP-99,994, R116301 (ID50 = 1.2 mumol/kg), and R115614 (ID50 = 1.8 mumol/kg) significantly reduced plasma leakage in the bladder (P<0.05), but not the trachea (P>0.05). R116301 (ID50 = 0.7 mumol/kg) and R115614 (ID50 = 1.2 mumol/kg) were able to inhibit the salivation response significantly (P<0.05). / R116301 and R115614 significantly reduced emesis induced by resiniferatoxin, motion, copper sulphate, and cisplatin (P<0.05), in the dose range between 23-70 mumol/kg, s.c. Both antagonists (100-300 nmol, i.c.v.) were also able to reduce cisplatin-induced emesis significantly (P<0.05), but only R116301 (10-300 nmol, i.c.v.) was able to significantly inhibit emesis induced by nicotine and copper sulphate (P<0.05). / The development of tachyldnin NK1 receptor antagonist aprepitant as an effective anti-emetic drug illustrates the importance of NK1 receptors in the emetic reflex. However, the exact anti-emetic mechanism of action is still unknown. The primary aim of the study was to investigate the relative contribution of centrally versus peripherally located NK1 receptors in the emetic reflex in Suncus murinus. The study also investigated the potential contribution of NK2 and NK3 receptors in emesis control. / The present studies demonstrated that R116301 and R115614 exhibited anti-emetic properties against various drugs, motion, and tachykinin receptor agonists. The studies also imply the existence of the classical SP subsite and the septide subsite of the NK1 receptors that are involved in the emetic reflex of Suncus murinus, which suggests that NK1 receptor antagonists that can block both subsites could become effective anti-emetic drugs. The present studies also demonstrated that both NK2 and NK3 receptors maybe involved in emesis control. It is possible that dual NK1/NK2 receptor antagonists or triple NK 1/NK2/NK3 receptor antagonists may have clinical potential as anti-emetic drugs besides the clinically used NK1 receptor antagonists. / The rank order of potency (based on pEC50 values) of tachykinin receptor agonists to contract Suncus murinus ileum was as follow: [Sar9Met(O2)11] substance P (SP) (8.1) > septide (7.9) (both NK1 receptor agonists) > neurokinin A (NKA) (7.7) > SP (7.6) > GR 64349 (NK2 receptor agonist) (7.0). For the NK1 receptor antagonists, the rank order of potency (based on pKB/pA2 values) to inhibit ileal contraction was: R116301 (7.8-8.2) ≈ R115614 (7.7-8.3) > CP-99,994 (6.4-7.3) against various NK1 receptor agonists. Furthermore, NK2 receptor antagonist saredutant (pA2 = 7.3) competitively antagonised GR 64349-induced ileal contraction. / When injected intracerebroventricularly, SP (100 nmol), septide, [Sar 9Met(O2)11] SP, NKA (all at 30 nmol), GR 64349 (10 and 30 nmol), and senktide (NK3 receptor agonist) (3-30 nmol) significantly induced emesis in Suncus murinus (P<0.05). They were also effective in inducing locomotor hyperactivity, ano-genital grooming, circling, face washing, hindlimb licking, scratching, and straub tail (3-30 nmol, P<0.05). R116301 and R115614 (both at 3 and 10 mumol/kg, s.c.) significantly antagonised some of the actions of the agonists including emesis, locomotor hyperactivity, ano-genital grooming, licking, scratching, and straub tail (P<0.05). Saredutant and NK3 receptor antagonist osanetant (both at 30 mumol/kg, s.c.) attenuated emesis induced by GR 64349 and senktide respectively (P<0.05). Saredutant (30 mumol/kg, s.c.) was also able to inhibit GR 64349-induced face washing and scratching, while osanetant (30 mumol/kg, s.c.) also significantly attenuated senktide-induced straub tail (P<0.05). / Cheng, Ho Man Frankie. / "September 2007." / Adviser: John A. Rudd. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4691. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 194-223). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Lau Hoi Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 134-157). / Abstracts in English and Chinese. / PUBLICATIONS BASED ON WORK IN THIS THESIS --- p.I / ABSTRACT --- p.II / ACKNOWLEDGEMENTS --- p.VI / TABLE OF CONTENTS --- p.VIII / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Emesis --- p.3 / Chapter 1.2.1 --- Introduction --- p.3 / Chapter 1.2.2 --- Retching & Vomiting --- p.3 / Chapter 1.2.3 --- Nausea --- p.4 / Chapter 1.2.4 --- Motor Components of Emetic Reflex --- p.5 / Chapter 1.2.4.1 --- Pre-ejection Phase --- p.5 / Chapter 1.2.4.2 --- Ejection Phase --- p.5 / Chapter 1.2.4.3 --- Post-ejection Phase --- p.6 / Chapter 1.2.5 --- Components of Emetic Reflex --- p.6 / Chapter 1.2.5.1 --- Area Postrema (AP) --- p.6 / Chapter 1.2.5.2 --- Nucleus Tractus Solitarius (NTS) --- p.7 / Chapter 1.2.5.3 --- Vomiting Centre --- p.8 / Chapter 1.2.5.4 --- Vestibular System --- p.10 / Chapter 1.2.5.5 --- Abdominal Visceral Afferents --- p.10 / Chapter 1.2.5.6 --- Forebrain --- p.11 / Chapter 1.2.6 --- Neurotransmitters & Receptors --- p.12 / Chapter 1.2.7 --- Anti-emetics --- p.13 / Chapter 1.3 --- Models of Nausea --- p.16 / Chapter 1.3.1 --- Introduction --- p.16 / Chapter 1.3.2 --- Conditioned Taste Aversion --- p.18 / Chapter 1.3.3 --- Pica Behaviour --- p.20 / Chapter 1.3.4 --- Studies of the Involvement of Vasopressin --- p.21 / Chapter 1.3.5 --- Tachygastria --- p.24 / Chapter 1.3.6 --- Locomotor Activity --- p.26 / Chapter 1.4 --- Markers of Neuronal Activity --- p.27 / Chapter 1.4.1 --- General Comments --- p.27 / Chapter 1.4.2 --- c-fos Expression as a Marker of Neuronal Activity --- p.28 / Chapter 1.4.2.1 --- What is c-fos? --- p.28 / Chapter 1.4.2.2 --- Regulation of c-fos Expression --- p.30 / Chapter 1.4.2.2.1 --- Calcium Response Element --- p.31 / Chapter 1.4.2.2.2 --- Serum Response Element --- p.32 / Chapter 1.4.2.3 --- Types of Receptors Involved in c-fos Expression --- p.32 / Chapter 1.4.2.4 --- Feasibility of Using c-fos Expression as Marker of Cellular Activity --- p.36 / Chapter 1.4.2.5 --- Identification of Emetic Pathway by c-fos Immunohistochemistry --- p.36 / Chapter 1.5 --- Aims & Objectives --- p.37 / Chapter CHAPTER 2 --- METHODS --- p.42 / Chapter 2.1 --- Animals --- p.42 / Chapter 2.1.1 --- Ferrets --- p.42 / Chapter 2.1.2 --- Suncus murinus --- p.42 / Chapter 2.2 --- Measurement of Animal Behaviour --- p.43 / Chapter 2.2.1 --- Experiment Design --- p.43 / Chapter 2.2.2 --- Recording of Animal Behaviour --- p.43 / Chapter 2.2.3 --- Calibration of Equipment Used to Record Spontaneous Locomotor Activity --- p.44 / Chapter 2.2.4 --- Behaviour Recorded by the Observer --- p.45 / Chapter 2.3 --- Administration of Drugs --- p.46 / Chapter 2.3.1 --- Ferrets --- p.46 / Chapter 2.3.1.1 --- General Comments --- p.46 / Chapter 2.3.1.2 --- Drug Antagonism Studies --- p.47 / Chapter 2.3.2 --- Suncus murinus --- p.47 / Chapter 2.3.2.1 --- General Comments --- p.47 / Chapter 2.3.2.2 --- Dose-Response Studies --- p.48 / Chapter 2.3.2.3 --- Drug Antagonism Studies --- p.48 / Chapter 2.4 --- c-fos Expression Studies in Ferret Brainstems --- p.50 / Chapter 2.4.1 --- Animals and Anaesthesia --- p.50 / Chapter 2.4.2 --- Perfusion and fixation --- p.50 / Chapter 2.4.3 --- Dehydration of brains --- p.51 / Chapter 2.4.4 --- Embedding of tissue --- p.52 / Chapter 2.4.5 --- Sectioning --- p.52 / Chapter 2.4.6 --- Staining --- p.52 / Chapter 2.4.7 --- Antibodies used --- p.55 / Chapter 2.4.8 --- Positive Control Slides --- p.55 / Chapter 2.5 --- Experimental Design and Statistics --- p.56 / Chapter 2.5.1 --- Randomization of Treatments --- p.56 / Chapter 2.5.2 --- Statistics --- p.57 / Chapter 2.5.2.1 --- Ferrets --- p.57 / Chapter 2.5.2.2 --- Suncus murinus --- p.59 / Chapter 2.6 --- Drugs and Chemicals Used --- p.60 / Chapter 2.6.1 --- Drugs Used --- p.60 / Chapter 2.6.2 --- Chemicals Used --- p.62 / Chapter CHAPTER 3 --- RESULTS --- p.63 / Chapter 3.1 --- Ferret --- p.63 / Chapter 3.1.1 --- "The Effect of Ondansetron and CP-99,994 on Emesis and Locomotor Activity Changes Induced by Cisplatin in the Ferret" --- p.63 / Chapter 3.1.2 --- The Effect of Domperidone on Emesis and Locomotor Activity Changes Induced by Apomorphine in the Ferret --- p.69 / Chapter 3.1.3 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Apomorphine in the Ferret" --- p.74 / Chapter 3.1.4 --- c-fos Expression Studies in Ferret Brainstems --- p.79 / Chapter 3.1.4.1 --- Cisplatin-treated Ferrets --- p.79 / Chapter 3.1.4.2 --- Positive Control Slides --- p.84 / Chapter 3.2 --- Suncus murinus --- p.88 / Chapter 3.2.1 --- The Emetic Potential of Nicotine and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.88 / Chapter 3.2.2 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Nicotine in Suncus murinus" --- p.92 / Chapter 3.2.3 --- The Emetic Potential of Copper Sulphate and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.95 / Chapter 3.2.4 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Copper Sulphate in Suncus murinus" --- p.98 / Chapter 3.2.5 --- The Emetic Potential of Cisplatin and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.101 / Chapter 3.2.6 --- The Effect of Ondansetron on Emesis and Locomotor Activity Changes Induced by Cisplatin in Suncus murinus --- p.104 / Chapter 3.2.7 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Cisplatin in Suncus murinus" --- p.107 / Chapter 3.2.8 --- "The Effects of Ondansetron and CP-99,994 on Locomotor Activity in Suncus murinus" --- p.110 / Chapter CHAPTER 4 --- DISCUSSION --- p.113 / Chapter CHAPTER 5 --- GENERAL SUMMARY --- p.130 / REFERENCES --- p.134