Publications by authors named "Nicholas MacInnes"

Dementia with Lewy bodies (DLB) accounts for 15-20% of the millions of people worldwide with dementia. In the current work we investigate the association between proteasome dysfunction and the development of cortical Lewy body pathology. Analysis of post-mortem cortical tissue indicated levels of the alpha-subunit of the 20S proteasome were significantly reduced in DLB cortex, but not Alzheimer's, in comparison to control and this reduction correlated with both the severity and duration of dementia.

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In vitro studies suggest that group III metabotropic glutamate (mGlu) receptors function as hetero-receptors to modulate GABA release within the globus pallidus. In the present study we examined this hypothesis in vivo, using microdialysis to assess the ability of locally infused group III mGlu receptor agonists to modulate KCl-evoked GABA release in the globus pallidus of anaesthetised rats. Extra-cellular levels of GABA in dialysate samples were assayed using High Pressure Liquid Chromatography (HPLC) coupled to electrochemical detection.

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Imidazoline I2 binding sites are heterogeneous in nature and have been observed in the brain of a number of species. Development of specific imidazoline I2 radioligands, such as [3H]2-BFI and [3H]BU224, that have a high affinity for the imidazoline I2 binding site, has enabled the central distribution of these sites to be mapped. Extensive studies have been conducted on the rat brain with a number of radioligands.

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The present study examined the ability of the selective imidazoline I(2)-site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway. Male Sprague-Dawley rats were injected with 12.5 microg 6-hydroxydopamine (6-OHDA) into the right median forebrain bundle to induce a unilateral lesion of the nigrostriatal tract.

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Chronic administration of I(2) ligands increases the density of central I(2) sites as measured in brain homogenates. Here, we have used autoradiography to examine whether the increase in I(2) site density induced by chronic administration of 2-(2-benzofuranyl)-2-imidazoline (2-BFI) is uniform across brain regions. We dosed rats with 2-BFI 7 mg/kg or with saline vehicle i.

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1. This study examined whether group III metabotropic glutamate (mGlu) receptor agonists injected into the globus pallidus (GP), substantia nigra pars reticulata (SNr) or intracerebroventricularly (i.c.

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The functional significance of imidazoline I2 binding sites is unknown but microdialysis studies have indicated that the administration of I2-site ligands leads to an increase in extracellular levels of monoamines. The specific I2-site ligand 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) generates a cue in drug discrimination, thereby indicating functional consequences of I2-site ligand binding. In the present work, we explored the ability of selective noradrenergic and serotonergic ligands to substitute for 2-BFI.

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1. The molecular nature and functions of the I(2) subtype of imidazoline binding sites are unknown but evidence suggests an association with monoamine oxidase (MAO). Rats can distinguish the selective imidazoline I(2)-site ligand 2-BFI from vehicle in drug discrimination, indicating functional consequences of occupation of these sites.

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