Despite their acknowledged efficacy, currently available antidepressants still demonstrate undesirable side effects, shortfalls in effectiveness and a delayed onset of action. All these agents act via monoaminergic mechanisms, although recent studies have begun to note the potential role of the cholinergic system as well as the amino acid pathways in affective isorders. It has been suggested that glutamate NMDA receptor activation may be involved in hippocampal degeneration seen in patients with depression, as well as contributing as a molecular target for the antidepressant action of known antidepressant drugs. Glutamate either separately or via the release of nitric oxide, regulates the release of various transmitters in the brain critical for affective state, e.g. monoamines (noradrenaline, dopamine), indoleamines (5HT), y-aminobutyric acid (GABA) and acetylcholine. The aim of this study was to investigate N-methyl-D-aspartate (I\IMDA) and muscarinic M1 receptor characteristics and also GABA and acetylcholine levels in a genetic animal model of depression, the Flinders Sensitive Line (FSL) rat, with respect to its control, viz. Flinders Resistant Line (FRL) rat, thereby establishing a possible role for the amino acid and cholinergic pathways in the hippocampus and frontal cortex, two brain areas implicated in depression. In addition, anxietylike behaviours were assessed using the open field and social interaction tests. A sensitive liquid chromatography tandem mass spectrometer (LC/MS/MS) method was used in the quantification of acetylcholine as well as high performance liquid chromatography with electrochemical detection (HPLG-EGD) for the quantification of GABA in the above-mentioned brain areas of FSL and FRL rats. NMDA and muscarinic M1 receptor characteristics were expressed in terms of receptor denSity (Bmax) and affinity (Kd) values and were performed using [3H]-MK801 (27.5 Gi/mmol) and quinuclidinyl benzilate (52.0 Gilmmol) for NMDA and M1 receptors, respectively. In addition, to provide evidence for face validity, behavioural assessments were routinely performed using the open field test and social interaction test. Significantly elevated levels of acetylcholine were found in the frontal cortex but with significantly reduced levels in the hippocampus of FSL rats. Cortical and hippocampal muscarinic receptor binding characteristics remained unchanged, while no differences with regard to GABA levels and NMDA receptor binding characteristics were noted in these brain areas. In concordance with studies from the literature, aversive and locomotor behaviour as measured in the open field test, provided evidence of anxiogenic behaviour in the FSL rat, evinced by significantly less social interaction than their FRL counterparts. In addition, evidence for a lack in general activity of the FSL rat in the open field was also noted. Our data therefore suggest the presence of a cholinergic dysfunction in both the frontal cortex and hippocampus of the FSL rat, although this is not accompanied by simultaneous changes in muscarinic M1 receptor binding in key limbic brain regions. Although increased cholinergic drive is a recognised characteristic of FSL rats and is representative of the model's' construct validity, we suggest that the depressive phenotype of these animals is not related to altered cholinergic activity in a single brain region, but instead involves various limbic brain regions, possibly being more dependent on opposing cholinergic deficits in the cortex and hippocampus. / Thesis (M.Sc. (Pharmacology)--North-West University, Potchefstroom Campus, 2009.

Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2008.

Despite their acknowledged efficacy, currently available antidepressants still demonstrate undesirable side effects, shortfalls in effectiveness and a delayed onset of action. All these agents act via monoaminergic mechanisms, although recent studies have begun to note the potential role of the cholinergic system as well as the amino acid pathways in affective isorders. It has been suggested that glutamate NMDA receptor activation may be involved in hippocampal degeneration seen in patients with depression, as well as contributing as a molecular target for the antidepressant action of known antidepressant drugs. Glutamate either separately or via the release of nitric oxide, regulates the release of various transmitters in the brain critical for affective state, e.g. monoamines (noradrenaline, dopamine), indoleamines (5HT), y-aminobutyric acid (GABA) and acetylcholine. The aim of this study was to investigate N-methyl-D-aspartate (I\IMDA) and muscarinic M1 receptor characteristics and also GABA and acetylcholine levels in a genetic animal model of depression, the Flinders Sensitive Line (FSL) rat, with respect to its control, viz. Flinders Resistant Line (FRL) rat, thereby establishing a possible role for the amino acid and cholinergic pathways in the hippocampus and frontal cortex, two brain areas implicated in depression. In addition, anxietylike behaviours were assessed using the open field and social interaction tests. A sensitive liquid chromatography tandem mass spectrometer (LC/MS/MS) method was used in the quantification of acetylcholine as well as high performance liquid chromatography with electrochemical detection (HPLG-EGD) for the quantification of GABA in the above-mentioned brain areas of FSL and FRL rats. NMDA and muscarinic M1 receptor characteristics were expressed in terms of receptor denSity (Bmax) and affinity (Kd) values and were performed using [3H]-MK801 (27.5 Gi/mmol) and quinuclidinyl benzilate (52.0 Gilmmol) for NMDA and M1 receptors, respectively. In addition, to provide evidence for face validity, behavioural assessments were routinely performed using the open field test and social interaction test. Significantly elevated levels of acetylcholine were found in the frontal cortex but with significantly reduced levels in the hippocampus of FSL rats. Cortical and hippocampal muscarinic receptor binding characteristics remained unchanged, while no differences with regard to GABA levels and NMDA receptor binding characteristics were noted in these brain areas. In concordance with studies from the literature, aversive and locomotor behaviour as measured in the open field test, provided evidence of anxiogenic behaviour in the FSL rat, evinced by significantly less social interaction than their FRL counterparts. In addition, evidence for a lack in general activity of the FSL rat in the open field was also noted. Our data therefore suggest the presence of a cholinergic dysfunction in both the frontal cortex and hippocampus of the FSL rat, although this is not accompanied by simultaneous changes in muscarinic M1 receptor binding in key limbic brain regions. Although increased cholinergic drive is a recognised characteristic of FSL rats and is representative of the model's' construct validity, we suggest that the depressive phenotype of these animals is not related to altered cholinergic activity in a single brain region, but instead involves various limbic brain regions, possibly being more dependent on opposing cholinergic deficits in the cortex and hippocampus. / Thesis (M.Sc. (Pharmacology)--North-West University, Potchefstroom Campus, 2009.

Using neutral and emotional faces as stimuli, the Emotional Continuous Performance Task (EMO-CPT) was designed to measure both “cold” and “hot” executive functions. It was predicted that neutral stimuli would be associated with “cold” circuit functions such as sustained attention and response speed, while emotionally-laden EMO-CPT stimuli would be associated with “hot” circuit functions such as emotional judgement and response inhibition. Twenty-one male and 56 female university students (M = 21.57 years; SD = 3.15) completed the EMO-CPT, Counting Stroop (CS), Balloon Analogue Risk Task (BART), Behaviour Rating Inventory of Executive Function (BRIEF), and a demographic survey. The EMO-CPT consisted of 240 trials counterbalanced into 8 separate blocks of neutral, happy, and angry faces, with 1500ms and 3000ms stimulus intervals. Principle axis factor analysis with orthogonal (varimax) rotation revealed “Sustained/Speed” (SS; Eigenvalue = 4.26) and “Accuracy/Inhibition” (AI; Eigenvalue = 2.49) factors accounting for 48.75% of the total variance. The SS factor was modestly correlated with the BRIEF Metacognitive Index (MI; r=.25), and both the Sustained/Speed factor (r=.27) and the Accuracy/Inhibition factor (r=.25) were modestly correlated with the BRIEF Behavioural Regulation Index (BRI). As predicted, “cold” Counting Stroop reaction time variables were related to the Sustained/Speed factor (r’s .30 to .36), and the “hot” BART adjusted inflations SD were related to the Accuracy/Inhibition factor (r = -.22). Correlated with the CS and BRIEF MI, the Sustained/Speed factor appeared to tap “cold” dorsal circuit functions, while the Accuracy/Inhibition factor appeared to be related to “hot” ventral circuit functions. / Graduate

Various needle trap devices (NTDs) with different designs for different applications have been developed during the past decade. A theoretical model on the fundamentals of the NTD was recently proposed, which employed the theory of frontal (gas-solid) chromatography to describe the sampling process, where a gaseous sample was continuously introduced into the sorbent bed. In this investigation, different types of sorbent particles with different dimensions were packed into the needle as adsorbents. The effect of particle dimension, which would affect the packing density and consequently the capacity, the extraction efficiency, and desorption efficiency of the NTD were experimentally investigated and the proposed theory was validated. The results demonstrated that NTDs packed with small particles possess higher extraction capacity and efficiency but much higher resistance to flow as well. The higher resistance did not necessarily result in poor desorption efficiency, because desorption efficiency was affected by both the sorbent bed structure and the desorption gas flow. The relationships observed among those physical parameters provide valuable guidance on how to design an NTD with high performance potential for future applications. For particulate sampling, it was found that NTDs packed with different particles presented high collection efficiency of the particulates being investigated, and the collection efficiency was dominated by the pore size and distribution of the sorbent bed packed inside the needle. Collection efficiency also increased with increase in solidity of the sorbent bed; the increase in humidity of the aerosol sample; and the decrease of sampling rate. The results also provide valuable guidance on the optimisation of needle trap for particulate collection.

Thesis (Ph.D.)--York University, 2006. Graduate Programme in Psychology. / Typescript. Includes bibliographical references (leaves 122-152). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR29500

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Thesis (M.A.)--University of Toronto, 2004. / Includes bibliographical references (leaves [33]-40).

Thesis (D.Phil (Social Work and Criminology))--University of Pretoria, 2005. / Includes abstract in English and Afrikaans. Bibliography.

Made available in DSpace on 2013-08-07T19:03:52Z (GMT). No. of bitstreams: 1 000400686-Texto+Completo-0.pdf: 699000 bytes, checksum: aa3d0c0c954908edec60e4747fe3ebe8 (MD5) Previous issue date: 2008 / The goal of this research is to develop and conduct a study on preliminary construct validity in an evaluation scale of the executive dysfunction in daily lives of adult individuals. The scale is an instrument of self- report that evaluates the prefrontal cortex coordination under superior cognitive abilities. The ages of the participants involved varied from 18 to 79 years old. The construct was chosen based on the demand, observed in the neurological clinic, to evaluate the daily lives of dysexecutives individuals. Content validity studies and a preliminary study of the construct validity show that the scale presents adequate psychometrical characteristics and can contribute to the daily lives rehabilitation of individuals that present executive dysfunctions due to neurological injuries or neuropsychiatric disorders. One hundred eighty one people from both genders and with no previous clinical neurological diagnosis participated in the factor analysis preliminary study. The study is considered preliminary because it is a projection of a future construct validity study with a higher number of participants and including individuals with neurological injuries in prefrontal regions. The preliminary study of the construct validity counted one hundred eighty one participants (average age of 37. 5 years old). The results indicated an accuracy index of 0. 86, considered to be precise. Solutions for four factors were found, this fact contributed to the initial project. The factor or dimensions were: time usage, obligation compliance, Hiatus between Theory and Practice and stimuli inhibition irrelevant throughout the attention/ concentration process.The results obtained on this research stimulate us to continue the studies about Construct Validity, Convergent-Divergent, Criteria and Normatization in order to perfect this scale that, in this initial step, seems more sensitive to the construct and adequate considering the Brazilian reality. Therefore, the results obtained indicate that we reached the initial goal of building and validating preliminarily a scale to evaluate the Executive Dysfunction in daily life. / Esta pesquisa teve por objetivo desenvolver e realizar um estudo de Validação de Construto preliminar de uma escala para avaliação da disfunção executiva na vida diária em indivíduos adultos. A escala é um instrumento de auto-relato que avalia a coordenação do córtex pré–frontal sob habilidades cognitivas superiores. As idades dos participantes variaram entre 18 a 79 anos de idade. O construto foi escolhido a partir da demanda observada na clínica neurológica para avaliação da vida diária de indivíduos com disfunção executiva. Estudos de validade de conteúdo e um estudo preliminar de validação de construto mostram que a escala apresenta adequadas características psicométricas e poderá contribuir para quantificação de resultados quanto à reabilitação da vida diária de indivíduos que apresentam disfunção executiva devido a lesões neurológicas ou transtornos neuropsiquiátricos. Do estudo preliminar de análise fatorial, participaram 181 pessoas de ambos os sexos e sem diagnóstico clínico neurológico. Este estudo é considerado preliminar por projetarmos um futuro estudo de validação de construto com número de participantes maior e incluindo indivíduos com lesões neurológicas em regiões pré–frontais. O estudo preliminar de Validação de Construto contou com 181 participantes (idade média 37,5 anos, d. p. =14,2). Os resultados indicaram o índice de precisão 0,86 considerado preciso. Foram encontradas soluções de quatro fatores, fato que corroborou com o projeto inicial. Os fatores ou dimensões foram os seguintes: uso do tempo, cumprimento de obrigações, hiatos entre a teoria e a prática e inibição de estímulos irrelevantes durante o processo da atenção /concentração.Os resultados obtidos nesta pesquisa nos estimulam a dar seguimento aos estudos de Validação de Construto, Concorrente-Divergente, Critério e Normatização para aperfeiçoamento desta escala que neste passo inicial se mostra sensível ao construto e adequada, a realidade brasileira. Portanto, os resultados obtidos indicam que alcançamos o nosso objetivo inicial de construir e validar preliminarmente uma escala para avaliação da disfunção executiva na vida diária.