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

Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line treatment for major depression, but require several weeks to elicit a clinical effect. One mechanism that may underlie this delay in SSRI action implicates the gradual desensitization of 5-HT1A autoreceptors, leading to enhanced firing and increasing serotonin (5-HT) at the synapse. I hypothesized that in absence of 5-HT1A autoreceptors, fluoxetine (FLX) would improve behavior faster and more effectively. To specifically knock out 5-HT1A receptors in 5-HT neurons, we crossed TPH2-CREERT2 and flx5HT1A-YFP mice to generate the flx1A mice, a tamoxifen-inducible conditional knockout. Tamoxifen-induced recombination in adult flx1A-/- mice induced YFP expression and reduced 5-HT1A receptor levels by over 90%, specifically in TPH-positive cells of the raphe. To test the response to sub-chronic SSRI treatment, the mice were treated for 9 days with SSRIs FLX or escitalopram and examined for anxiety and depression-like behavior using multiple tests, including the novelty suppressed feeding test (NSF) that responds to chronic but not acute SSRI treatment. Subchronic FLX treatment had no effect in flx1A +/+ control mice, but resulted in an unexpected anxiogenic effect in flx1A -/- littermates, in both the NSF and elevated plus maze tests. Subchronic treatment with escitalopram also increased anxiety-like behavior in the NSF in flx1A-/-, but not wild-type mice. To determine whether FLX treatment differentially affected brain activity in these mice, the number of FosB-stained cells was determined as an index of chronic activation. In flx1A -/- vs. +/+ mice, the number of FosB-positive cells was reduced in several brain regions linked to anxiety and depression including hippocampus and entorhinal cortex, and FLX III treatment reduced activation in the flx1A +/+ compared to -/- mice these areas and in 5-HT neurons of the median raphe nucleus. These results suggest that in the absence of 5-HT1A autoreceptors, SSRIs have a pro-anxiety effect that may involve reduced inactivation anxiety-related brain regions.