The monoamines play important roles as neurotransmitters both centrally and peripherally, and are believed to play a key role in a number of pathological conditions such as Parkinson's disease, schizophrenia, drug addiction, and mood disorders, which has driven many years of research, resulting in a relatively good understanding of the neurochemistry of this group of amines. [n contrast, relatively little is known about the role of a second class of endogenous amines, the 'trace amines, that share substantial overlap with the monoamines. For 30 years the trace amines, have also been thought to be associated with affective behaviour, paranoid chronic schizophrenia and depression. However, until the recent discovery of a novel family Gprotein- coupled receptors (GPCRs), with high affinity for the trace amines, research was restricted. One member of this family, trace amine 1 receptor (TA1) is functional in both rodents and man, and is expressed widely throughout the brain of the mouse, rat and human. The functional role of the TAl receptor in the mammalian brain was therefore the focus of the current project. In order to investigate the function of the TAl receptor, two specific TAl receptor agonists were used, kindly provided by Hoffman La Roche. As the TAl receptor has been implicated in the neuropathophysiology of several psychiatric disorders, such as ADHD and schizophrenia, which are characterised by substantial and debilitating deficits in cognitive performance, initial experiments aimed to assess for any effect of the TAl agonists on cognitive performance in laboratory rodents. In part, the association between the TAl receptor and mental disorders is based on evidence suggesting an interaction with monoamine neurotransmission. However, previously reported findings from in vitro studies do not support a mechanism of interaction comparable with results from in vivo studies. Therefore later experiments investigated the relationship between TAl and monoamine neurotransmission in vivo. Initial experiments focused on the interaction between TAl activation and behaviours induced by psychostimulants known to alter monoamine function, and subsequent investigation examined the possible mechanisms involved using in vivo microdialysis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:594216 |
| Date | January 2013 |
| Creators | Atkinson, Daniel Edward |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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