This thesis addresses the effects of pharmacological manipulations of brain 5- hydroxytryptamine (5-HT, serotonin) and it's precursor, tryptophan, on appetite and mood in humans. Chapter 1 is a presentation of the literature reviewed in order to carry out the studies contained within this thesis. General methods are described in Chapter 2; these include biochemical methods for analysis of plasma tryptophan, and measures and assessment methodologies for analysis of appetite and mood. This chapter also contains a pilot study of the methodology adopted for lowering plasma tryptophan levels. The first experiment (Chapter 3) examines the effects of calorie controlled dieting on plasma tryptophan, mood and appetite using a longitudinal design. Dieters were compared with a matched control group, and the results demonstrated that whilst dieting does not appear to alter mood or responses to food in a laboratory setting, it does lower levels of plasma tryptophan compared with baseline and with controls. In view of the confounding variables of dieting on mood and appetite, the second experiment (Chapter 4) examined the effects of an acute, laboratory based depletion of plasma tryptophan on these parameters in healthy female volunteers acting as their own controls. Significant depletion of plasma tryptophan was not associated with alterations in mood or appetite. The third experiment (Chapter 5) addresses the issue of predisposing factors in the effects of tryptophan depletion on mood and appetite. This was carried out with a group of women who had recovered from an eating disorder (bulimia nervosa). These subjects were acting as their own controls but were also compared directly with the non-clinical group of subjects from the previous experiment. This experiment demonstrated interesting differences in the eating behaviour of the two groups, and a significant difference in baseline levels of total plasma tryptophan. There were, however, no effects of tryptophan depletion on mood or appetite in the women who had recovered from bulimia nervosa. In view of the apparent lack of effect of tryptophan depletion on mood or appetite, the remaining two experiments examine the role of specific 5-HT receptor subtypes in the control of appetite. Chapter 6 examines the effect of meta-chlorophenylpiperazine (mCPP), a 5-HT_2C receptor agonist on appetite, and Chapter 7 examines the effect of 5-HT₃ receptor blockade on amphetamine anorexia. Whilst the data from these experiments do not support a role for these receptor subtypes in appetite, it is suggested that this is a potentially fruitful area for future research. The results generated by the above experiments are discussed in Chapter 8 in the light of other research findings. The methodologies adopted for these experiments and the implications of these studies for future research are discussed.

Despite substantial progress in the area of depression research, the current treatments for Major Depressive Disorder (MDD) remain suboptimal. Therefore, various medications are often used as augmenting agents in pharmacotherapy of treatment-resistant MDD. Despite the relative clinical success, little is known about the precise mechanisms of their antidepressant action. The present work was focused on describing the effects of three drugs with distinctive pharmacological properties (pramipexole, aripiprazole, and quetiapine) on function of the monoaminergic systems involved in the pathophysiology and treatment of MDD. Reciprocal interactions between the monoamines serotonin, norepinephrine, and dopamine systems allow the drugs targeting one neuronal entity to modify the function of the other two chemospecific entities. Electrophysiological experiments were carried out in anaesthetized rats after 2 and 14 days of drug administration to determine their immediate and the clinically-relevant long-term effects upon monoaminergic systems. Pramipexole is a selective D2-like agonist with no affinity for any other types of receptors. It is currently approved for use in Parkinson’s disorder and the restless leg syndrome. Long-term pramipexole administration resulted in a net increase in function of both dopamine and serotonin systems. Aripiprazole is a unique antipsychotic medication. Unlike all other representatives of this pharmacological class that antagonize D2 receptor, this drug acts as a partial agonist at this site. Chronic administration of aripiprazole elevated the discharge rate of the serotonin neurons, presumably increasing the overall serotonergic neurotransmission. Like aripiprazole, quetiapine is one of three atypical antypsicotic drugs approved for use in MDD. Prolonged administration of quetiapine led to a significant increase in both noradrenergic and serotonergic neurotransmission. Importantly, the clinically counter-productive decrease in the spontaneous firing of catecholaminergic neurons, induced by SSRIs, was overturned by the concomitant administration of both aripiprazole and quetiapine. The increase in serotonergic neurotransmission was a consistent finding between all three drugs studied herein. In every case this enhancement was attained in a distinctive manner. Understanding of the precise mechanisms leading to the amplification/normalization of function of monoamines enables potential construction of optimal treatment strategies thereby allowing clinicians greater pharmacological flexibility in the management of depressive symptoms.

<p>Selective serotonin re-uptake inhibitors (SSRIs) are a new class of antidepressants used mainly for the treatment of depression and other forms of related disorders. There are a number of side effects associated with these drugs which include loss of weight, sexual dysfunction, nervousness and nausea. A fast and reliable detection method such as biosensing for the determination of the SSRIs metabolic profile is therefore essential for the appropriate dosing of these drugs. Biosensors for the determination of the SSRIs biotransformation were prepared with cytochrome P450 (2D6) isoenzyme and poly (anilinonapthalene sulfonic acid) film electrochemically deposited on gold.</p>

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 111-134).

Thesis (Ph.D.)--Kent State University, 2009. / Title from PDF t.p. (viewed Apr. 15, 2010). Advisor: J. David Glass. Keywords: Suprachiasmatic nucleus; serotonin; nonphotic; arginine vasopressin; hamster. Includes bibliographical references (p. 91-111).

Thesis (Ph. D. in Neuroscience)--Vanderbilt University, Aug. 2005. / On t.p. "C̳" is subscript. Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--Florida State University, 2006. / Advisor: Natalie Sachs-Ericsson, College of Arts and Sciences, Dept. of Psychology. Title and description from dissertation home page (viewed Sept. 19, 2006). Document formatted into pages; contains viii, 46 pages. Includes bibliographical references.

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Magister Scientiae - MSc / Selective serotonin re-uptake inhibitors (SSRIs) are a new class of antidepressants used mainly for the treatment of depression and other forms of related disorders. There are a number of side effects associated with these drugs which include loss of weight, sexual dysfunction, nervousness and nausea. A fast and reliable detection method such as biosensing for the determination of the SSRIs metabolic profile is therefore essential for the appropriate dosing of these drugs. Biosensors for the determination of the SSRIs biotransformation were prepared with cytochrome P450 (2D6) isoenzyme and poly (anilinonapthalene sulfonic acid) film electrochemically deposited on gold. / South Africa