Characteristics of the wave energy resource at the Atlantic marine energy test site

The wave energy industry is progressing towards an advanced stage of development, with consideration being given to the selection of suitable sites for the first commercial installations. An informed, and accurate, characterisation of the wave energy resource is an essential aspect of this process. Ireland is exposed to an energetic wave climate, however many features of this resource are not well understood. This thesis assesses and characterises the wave energy resource that has been measured and modelled at the Atlantic Marine Energy Test Site, a facility for conducting sea trials of floating wave energy converters that is being developed near Belmullet, on the west coast of Ireland. This characterisation process is undertaken through the analysis of metocean datasets that have previously been unavailable for exposed Irish sites. A number of commonly made assumptions in the calculation of wave power are contested, and the uncertainties resulting from their application are demonstrated. The relationship between commonly used wave period parameters is studied, and its importance in the calculation of wave power quantified, while it is also shown that a disconnect exists between the sea states which occur most frequently at the site and those that contribute most to the incident wave energy. Additionally, observations of the extreme wave conditions that have occurred at the site and estimates of future storms that devices will need to withstand are presented. The implications of these results for the design and operation of wave energy converters are discussed. The foremost contribution of this thesis is the development of an enhanced understanding of the fundamental nature of the wave energy resource at the Atlantic Marine Energy Test Site. The results presented here also have a wider relevance, and can be considered typical of other, similarly exposed, locations on Ireland’s west coast.

Novel roles for the GABAB receptor in anxiety and cocaine addiction

The GABAB receptor has been postulated as a possible drug target in the treatment of anxiety disorders and cocaine addiction. Indeed, a wealth of preclinical data is emerging that has shown that mice lacking functional GABAB receptors display a highly anxious behaviour across a range of behavioural models of anxiety. Additionally, novel compounds that act by altering the allosteric conformation of the GABAB receptor to a more active state; the GABAB receptor positive modulators, have been repeatedly demonstrated to have anxiolytic effects in animals. In addition to being a putative anxiolytic drug target, the GABAB receptor has been identified as a novel target for antiaddictive therapies. Indeed GABAB receptor positive modulators have been demonstrated to have anti-addictive properties across a broad variety of behavioural paradigms. Despite these findings, several gaps in our knowledge of the role played by the GABAB receptor in both anxiety and drug abuse disorder exist. The aim of this thesis was to use preclinical animal models in an effort to further probe the role played by the GABAB receptor in anxiety and addiction. Our studies initially examined the role played by the GABAB receptor in the neurodevelopmental processes underpinning of anxiety. Our studies demonstrated that treating mouse pups in early life with the GABAB receptor agonist baclofen produced an anxious phenotype in adult life, whereas treatment with the GABAB receptor antagonist CGP52432 produced no effects on adult behaviour. Further to this, we examined whether the anxious behaviour induced by early life blockade of the serotonin reuptake transporter was dependant on alterations in GABAB receptor function. Our studies however revealed no effect of early life selective serotonin reuptake inhibitor treatment on adult life baclofen sensitivity. The next issue addressed in this thesis is the characterization of the effects of a GABAB receptor positive modulator and a GABAB receptor antagonist in a behavioural model of conditioned fear behaviour. These novel classes of GABAB receptor ligands have been considerably less well characterized in this facet of preclinical anxiety behaviour than in terms of innate anxiety behaviour. Our study however revealed that the GABAB receptor positive modulator GS39783 and the GABAB receptor antagonist CGP52432 were without effect on the acquisition, expression or extinction of conditioned fear in our model. The next element of this thesis dealt with the characterization of a novel mouse model, the GABAB(2)- S892A mouse. This mouse has been engineered to express a form of the GABAB(2) receptor subunit wherein the function determining serine phosphorylation site cannot be phosphorylated. We initially tested this mouse in terms of its GABAB receptor function in adult life, followed by testing it in a battery of tests of unconditioned and learned anxiety behaviour. We also examined the behavioural and molecular responses of the GABAB(2)-S892A mouse to cocaine. All of our studies appear to show that the GABAB(2)-S892A mouse is indistinguishable from wildtype controls. The final aim of the thesis was to investigate the behavioural and molecular sensitivity of the GABAB(1) subunit isoform null mice, the GABAB(1a) -/- and GABAB(1b) -/- mice to cocaine. Our studies revealed that these mice display differing behavioural responses to cocaine, with the GABAB(1a) -/- mouse displaying a hypersensitivity to the acute locomotor effects of cocaine, while the GABAB(1b) -/- displayed blunted locomotor sensitisation to cocaine.