This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

by Ho, Chung Shun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves [304-328]). / Chapter CHAPTER 1 --- REVIEW ON SODIUM EXCRETION / Chapter L --- Sodium excretion --- p.1-1 / Chapter II. --- Cellular mechanism of sodium reabsorption --- p.1-3 / Chapter III. --- Sensors monitoring ECF volume --- p.1-6 / Chapter IV. --- Factors affecting natriuresis: / Glomerular filtration rate --- p.1-8 / Renal physical forces --- p.1-8 / Sympathetic nervous system --- p.1-10 / Renal dopamine --- p.1-12 / Renin-angiotensin system --- p.1-14 / Aldosterone --- p.1-16 / Renal prostaglandins --- p.1-17 / Renal kallikrein-kinin system --- p.1-18 / Natriuretic peptides --- p.1-19 / Endogenous sodium transport inhibitor --- p.1-21 / Vasopressin --- p.1-22 / Endothelins --- p.1-23 / Endothelin-derived relaxing factor --- p.1-25 / Other hormones --- p.1-25 / Chapter V. --- Conclusion --- p.1-27 / Chapter CHAPTER 2 --- MEASUREMENT OF ENDOGENOUS SODIUM TRANSPORT INHIBITORS / Chapter I. --- Literature review: --- p.2-1 / Pretreatment and purification procedures prior to ESTI measurement --- p.2-1 / Methods of measuring ESTI --- p.2-3 / "Inhibition of purified Na, K-ATPase activity" / Inhibition of sodium pump on intact cells or tissues / Biological effects of sodium pump inhibition / Immunoreactivity with anti-digoxin /anti-ouabain antibodies / Chapter II. --- Method of measurement of ESTI in this study: / Principles of methods --- p.2-11 / Materials and methods --- p.2-14 / Results --- p.2-24 / Discussion --- p.2-53 / Chapter CHAPTER 3 --- MEASUREMENT OF URINARY FREE DOPAMINE / Chapter I. --- Literature review / Properties of dopamine for measurement methods --- p.3-1 / Preservatives used in the urine collection --- p.3-3 / Sample pretreatment procedure before --- p.3-6 / measurement --- p.3-8 / Methods of measurement / Bioassays / Colorimetric method / Fluorometric methods / Radioimmunoassays / Radioenzymatic method / Chromatographic methods --- p.3-16 / Concluding remarks / Chapter II. --- Method of measurement in this study / Principle of the method --- p.3-17 / Materials and methods --- p.3-18 / Results --- p.3-23 / Discussion --- p.3-54 / Chapter CHAPTER 4 --- CROSS SECTIONAL STUDIES IN THE HUMAN / Chapter I. --- Introduction --- p.4-1 / Chapter II. --- Relationship of urinary sodium excretion and plasma ESTI in medical students / Materials and methods --- p.4-2 / Results --- p.4-3 / Discussion --- p.4-6 / Chapter III. --- Excretion of urinary electrolytes and natriuretic factors in young Chinese females / Materials and methods --- p.4-7 / Results --- p.4-8 / Discussion --- p.4-11 / Chapter IV. --- Urinary sodium / DA relationship in Chinese normotensives and hypertensives --- p.4-13 / Materials and methods / Results --- p.4-14 / Discussion --- p.4-17 / Chapter V. --- Urinary DA excretion and plasma ESTI in normotensive and hypertensive NIDDM patients / Materials and methods --- p.4-20 / Results --- p.4-23 / Discussion --- p.4-33 / Chapter CHAPTER 5 --- VOLUME EXPANSION STUDIES IN THE HUMAN / Chapter I --- Introduction --- p.5-1 / Chapter II. --- Volume expansion by headout water immersion / Materials and methods --- p.5-3 / Results --- p.5-5 / Discussion --- p.5-11 / Chapter III. --- Volume expansion by saline infusion / Materials and methods --- p.5-16 / Results --- p.5-19 / Discussion --- p.5-29 / Chapter IV. --- Oral salt loading with free diet / Materials and methods --- p.5-36 / Results --- p.5-38 / Discussion --- p.5-49 / Chapter V. --- Oral salt loading under controlled diet / Materials and methods --- p.5-53 / Results --- p.5-54 / Discussion --- p.5-64 / Chapter CHAPTER 6 --- STUDIES ON THE EFFECTS OF SALT LOADING IN THE RAT / Chapter I. --- Introduction --- p.6-1 / Chapter II. --- Temporal relationship between excretions of DA and ESTI during salt loading in the rat / Materials and methods --- p.6-2 / Results --- p.6-3 / Discussion --- p.6-6 / Chapter III. --- Roles of DA and ESTI in natriuresis in rats treated with carbidopa / Materials and methods --- p.6-8 / Results --- p.6-9 / Discussion --- p.6-14 / Chapter CHAPTER 7 --- CONCLUSION / Measurement of ESTI --- p.7-2 / Measurement of urinary free DA --- p.7-5 / Cross sectional studies in human --- p.7-7 / Volume expansion studies in human --- p.7-11 / Studies on the effects of salt loading in the rat --- p.7-16 / Summary --- p.7-18

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (doctoral)--University of Turku. / Bibliography: p. 100-115.

It is well established that chronic treatment with neuroleptic agents which selectively block dopamine (DA) receptors in the brain leads to the development of DA receptor supersensitivity. However comparing the degree and duration of the changes in receptor sensitivity obtained by different investigators has been extremely difficult, because of the numerous differences that exist in individual methods of producing and examining DA receptor supersensitivity. By examining the DA receptor supersensitivity that ensues following chronic treatment with different doses and durations of pimozide, at various intervals after withdrawal from treatment, the overall parametric changes can be more directly compared. To measure the changes in DA receptor sensitivity following chronic pimozide treatment, both behavioral (d.-amphetamine-induced locomotor activity; apomorphine-induced stereotypy) and biochemical (DA receptor binding assay) techniques were utilized. With increasing doses of chronic pimozide treatment, the degree and duration of the resulting DA receptor supersensitivity increased as measured both behaviorally and biochemically. Similarily, the longer durations of chronic pimozide treatment had a greater effect on the degree and duration of the increased DA receptor sensitivity than did the shorter durations of treatment. Correlations were found between the biochemical and behavioral results both between groups of animals treated chronically with different doses and durations of pimozide and within individual groups of animals. In addition, the changes in receptor sensitivity following chronic pimozide treatment was due to an increase in the number of DA receptors with no change in the affinity of these receptors to DA. These results following chronic treatment with neuroleptics demonstrate that the behavioral supersensitivity observed in animals in response to either the direct DA agonist apomorphine or the indirect DA agonist d-amphetamine, may be a result of an increased number of DA receptors. Finally, the supersensitive DA receptors that develop as a result of chronic treatment with neuroleptics are discussed with regard to their possible relevance as an animal model of the iatrogenic disease, tardive dyskinesia, observed clinically in schizophrenic patients withdrawn from neuroleptic therapy. / Medicine, Faculty of / Graduate

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2003. / Härtill 4 uppsatser.

The neurotransmitters serotonin (5-HT) and dopamine (DA) play roles in eating disorders, mood disorders, such as depression and anxiety, and in the regulation of locomotion. The 5-HT2C receptor is one of fourteen 5-HT receptor subtypes that is expressed in regions of the brain including the hippocampus, amygdala, dorsal striatum, nucleus accumbens (NA) and substantia nigra, and is therefore implicated in behaviours and disorders associated with these regions. 5-HT has been shown to exert both a tonic and phasic inhibitory control, through the 5-HT2C receptor, on the firing rate and bursting activity of DA-containing neurones in the ventral tegmental area which enhances DA release in the NA and prefrontal cortex. In addition, the 5-HT2C receptor is under the control of a monophasic diurnal rhythm and is in a position to alter circadian regulation and behaviour due to its expression in the suprachiasmatic nucleus (the light entrainable oscillator (LEO)). It was hypothesised that elevating expression of the 5-HT2C receptor would have a detrimental effect on mood and cause hypolocomotion while reducing 5-HT2C receptor expression would improve mood, cause hyperphagia, obesity and hyperlocomotion. In order to investigate these hypotheses mouse models that either over- or under-expressed the 5-HT2C receptor were implemented. The 5-HT2C receptor expression pattern and levels were confirmed in all mouse lines. A behavioural phenotype of hypolocomotion and increased anxiety in the 5-HT2C receptor over-expressing mice and hyperphagia, obesity and hyperlocomotion in the 5-HT2C receptor under-expressing mice were found the latter is conistent with current literature. During backcrossing of the mouse lines onto the C57Bl/6 genetic background the abnormal behavioural phenotypes were lost suggesting that 5-HT2C receptor function is particulary sensitive to the genetic background on which it is being expressed. In response to altered expression levels of 5-HT2C receptor, compensatory alterations were found in the 5-HT system, with an inverse relationship existing between both the 5-HT1A receptor mRNA expression levels and 5-HT release in the hippocampus with the expression levels of the 5-HT2C receptor. Over-expression of 5-HT2C receptor appears to inhibit DA release in the cortex. The circadian experiments showed that under-expressing the 5-HT2C receptor did not alter the regulation of the food entrainable oscillator and there was a suggestion that the regulation of the LEO was affected. In summary, these results demonstrate that altered expression of 5-HT2C receptors results in abnormal behaviours consistent with its role in psychiatric disorders, but that the outcome is dependent on the genetic background.