Obsessive-compulsive disorder is a chronic psychiatric disease. It seriously limits the quality of life of patients. Treatment of OCD is not yet fully successful and still many patients are left with debilitating symptoms without functioning medication. Animal models of genetic, behavioral, pharmacological, and optogenetic origins are beneficial in the achievement of new understandings of the disease. Chronic sensitization of serotonin 1A and 7-receptors with an agonist 8-OH-DPAT ((8- hydroxy-2-(di-propylamino)-tetralin hydrobromide) induces perseverative and compulsive behaviors, which is considered to constitute an animal model of OCD. In this thesis, the 8-OH- DPAT model has been tested in the active place avoidance task on Carousel maze to provide information about the model on learning. Second, this model is used to determine, whether co- administration of memantine or riluzole alleviates the cognitive and learning deficits of this model. To uncover these effects, an active place avoidance task on a Carousel maze was used. Measured criteria were total distance, entrances to the shock sector, total number of shocks, and median speed after the shock. During habituation, the animals were sensitized to 8-OH-DPAT (with a control group that did not receive 8-OH-DPAT but only saline). In an...

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There is a current lack of accurate tools to determine the concentration of cyanobacteria in situ.  Besides, cyanobacterial blooms have to be carefully monitored in reservoirs as they are more frequent because of climate change and can lead to potential released of toxins, along with other components. This project investigates the possible use of fluorescent probes to measure the concentration of different types of organic matter released by the algae. Three different species of toxic cyanobacteria were chosen to carry out this research as they are representative of the local harmful blooms found across Australia. Furthermore, the efficiency of two different chemicals (powdered activated carbon, also known as PAC, and alum) used in drinking water treatment plants were investigated, in order to determine a method for automatic dosage adjustment in water treatment plant. The organic matter was characterized by LC-OCD and fluorescence spectroscopy and statistical analysis such as principal component analysis was performed on the generated data. General characterization of the different species was firstly performed and globally, similar comportments were observed among the three cyanobacteria species. There is indeed a general increase in the release of organic material throughout the cell’s growth phase. Results from the jar tests showed that PAC mainly targeted humic-like substances and building blocks, which are middle size particles. The average removal rate obtained was 40µg/L per mg/L of PAC added into the water. Therefore, there is indication that the decreased efficiency for the removal of the taste and odor compounds observed in certain plants can be partially attributed to direct competition of organic matter adsorption onto PAC instead of a blockage of the PAC pores by larger particles. On the other hand, alum was able to remove large particles, particularly biopolymers and also humic-substances. However, a great increase of the low molecular weight molecules at very high doses of alum was seen, which suggest that a too high dose of alum is toxic for the algae cells. Based on the bench scale testing the recommended dose of 50 mg/L seems to be optimum for the studied water treatment plant. Specific ultraviolet absorbance and dissolved organic carbon measurements were also investigated and good correlations were found between the concentration of humic-like substances and absorbance, confirming that they are good measure to assess the content of organic matter in the water. However, as the slope coefficient of the linear trend varied between the species, it was not possible to obtain a common conversion factor for all the species. Finally, one fluorophore was found in common to all the samples and is characterized by the excitation-emission wavelength: 240/440 nm. Correlations with the chromatography’s results were investigated and this component seems to match the biopolymers and humic-like substances concentrations. Furthermore, its intensity decreases continuously with the addition of PAC whereas a drop was observed at the lower doses of alum. In regards on these findings, a method for automatic chemicals dosing from the fluorescence measures was proposed. / Detta examensarbete handlar om hur dricksvattenkvalitet kan kontrolleras och övervakas i vattenreningsverk. Nu existerar  inte någon exakt metod för att bestämma koncentrationen av cyanobakterier i vatten då det finns många olika arter. Men det är viktigt att övervaka algers tillväxt in i vattenreningsverk för de kan släppa ut skadliga ämnen till dricksvattnet. De tre arter som studerats i detta projekt är giftiga. Det organiska materialet i råvattnet kan också blockera membranporer eller leda till n biprodukter, som är cancerframkallande. Till sist konkurrerar några organiska substansen med smak- och luktföreningar för adsorptionsställena hos det pulverformiga aktiverade kolet. Därför är smaken och luktföreningarna inte väl borttagna, vilket leder till kundernas klagomål. Cyanobakterier måste övervakas noggrant.                            För att bestämma biologisk och kemisk egenskap hos vatten används flera tekniker för närvarande. I examensarbetet har undersökningar med vätskekromatografi och fluorescensteknik företagits. Kromatografi användes för att klassificera den organiska substansen i mindre grupper: biopolymerer, humus substanser, byggstenar och neutralmolekyler med låg molekylvikt (LMVN). Statistisk analys med R, inklusive huvudkomponentanalys företogs på insamlade data. Fluorescensdata registrerades också och visas i en excitationsutsläppsmatris.                            Experimenten reproducerade en behandlingsprocess och undersökte effektiviteten hos två kemikalier: pulveriserat aktivt kol (PAK) och alun. Resultaten visade att humusämnen   och dess byggstenar var väl borttagna av PAK medan även biopolymerer och humusämnen var väl bortagna av alun. Emellertid var en för hög dos av alun skadlig eftersom det ledde till en ökad frisättning av LMVN. I synnerhert kunde PAK ta bort 40µg/L av både humusämnen och dess byggstenar per mg/L av PAK tillagd. Det föreslår att de är de viktigaste konkurrenterna och att endast direkt konkurrens för adsorptionsställena sker. Om det fanns blockeringsfenomen, skulle det också finnas en minskning för biopolymererna. Den optimala doseringen av alun som bestämdes för det undersökta vattenreningsverket var 50 mg/L. Det kunde ta bort 60-70% av biopolymerer och 40-50% av humusämnen.                            Specifik ultraviolett absorbans och fluorescens registrerades. Båda visade riktigt bra korrelationer med humusämnen, vilket gör de till bra verktyg för att bedöma vattenkvaliteten. Men det kräver fortfarande att arten av cyanobakterie urskiljs eftersom koefficientens lutningar var olika. De kan därför vara ett verktyg för att mäta koncentrationen av organisk material, men arten måste vara känd. Fluorescencedata visade en topp vid 440 nm. En parallellfaktoranalys utfördes på data och endast en komponent hittades gemensam i alla prover. Därför studerades den maximala fluorescensintensiteten hos denna komponent. Å ena sidan kunde vi observera en kontinuerlig minskning av intensiteten när PAK tillsattes. Det är därför möjligt att veta hur man justerar den kemiska doseringen från fluorescensintensiteterna. I slutet av examensarbetet föreslås en metod för automatisk kemisk dosering. Fluorescensprober kan ännu inte exakt indikera cellkoncentrationen. Men med flera sonder som riktar sig till olika våglängder kan de redan vara till stor hjälp för styrning vid vattenverk.

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Le Trouble obsessionnel-compulsif (TOC) de l’enfant et de l’adolescent est un trouble fréquent mais encore peu reconnu. Le traitement de première intention est la thérapie cognitive et comportementale (TCC). Les objectifs de cette étude sont de démontrer la faisabilité d’un protocole de TCC en population clinique et de montrer l’évolution symptomatique pendant 18 mois. Neuf patients présentant un TOC âgés de 6 à 16 ans ont reçu 12 séances hebdomadaires de TCC. Une évaluation est réalisée avant et après le traitement puis tous les 6 mois pendant 18 mois, elle comprend la mesure des TOC (CY BOCS), également des symptômes anxieux (ECAP), de dépression (CDI), une échelle de fonctionnement global (C GAS) et d’amélioration (CGI). Trois subtests du WISC IV permettent d’analyser les capacités attentionnelles. Résultats : les patients s’améliorent de 46% à la CY BOCS après la TCC, de 69% à 18 mois. Les variations intra-individuelles montrent des profils évolutifs différents : réponse très rapide puis rémission, amélioration retardée suivie de rémission ou amélioration puis rechute. Un seul patient n’est pas répondeur. Un changement psychologique dans une optique différentielle et intra individuelle, par des techniques de ré échantillonage (Bootstrap) et de comparaison des profils (test de Kolmogorov-Smirnof) est observé pour les patients les plus sévèrement atteints initialement. Conclusions : Un protocole de TCC dans le TOC de l’enfant et de l’adolescent est réalisable en population clinique. L’efficacité est montrée et se poursuit pendant les 18 mois. La TCC permet une amélioration globale (CGI, C GAS), symptomatique (CY BOCS, ECAP, CDI) et cognitive (WISC IV). / Pediatric obsessive-compulsive disorder (OCD) is a frequent but a not usually recognized trouble. The first –line treatment is cognitive-behavioral therapy (CBT). Objective : To demonstrate the feasibility of CBT protocol delivered in an outpatient community-based clinic and to evaluate clinic symptoms at 18 months follow-up. Nine participants (age 6-16 years) received 12 CBT weekly sessions. Assessment is realized at pre and post treatment, and every 6 months during 18 months, including symptoms of TOC (CY BOC), of anxiety(ECAP), of depression ((CDI), global functioning (C GAS) and improvement (CGI). Three WISC IV subtests allow attentional capacity analysis. Results: patients improvements are : 46% at post treatment, and 69% at 18 months follow up. The intra-individual variations show differents evolutionary profiles : quick response and remission, delayed improvement followed by remission or improvement followed by relapse. Only one is non responder. A psychological change in a differential and intra-individual optical, with sample rate (Bootstrap) and profiles comparaison (test de Kolmogorov-Smirnof) is observed for the pre treatment more severe patients. Conclusions : CBT protocol of OCD in children and adolescent is feasible in community-base clinic. Efficiency is showed and continues during 18 months. CBT allows global (CGI, C GAS), symptom (CY BOCS, ECAP, CDI) and cognitive (WISC IV) improvements.

Obsessive–compulsive disorder (OCD) is a psychiatric condition that is characterized by two main symptom cohorts, namely recurrent inappropriate thoughts (obsessions) and seemingly purposeless repetitive motor actions (compulsions). In 70% of cases, the condition only re–sponds to chronic, but not sub–chronic, high dose treatment with the selective serotonin reup–take inhibitors (SSRIs), such as fluoxetine and escitalopram. This indicates a role for hyposero–tonergic functioning in the primary brain areas involved in OCD, namely the components of the cortico–striatal–thalamic–cortical (CSTC) circuit which include the prefrontal cortex, the basal ganglia, and the thalamus. A number of studies have demonstrated a lower serotonin trans–porter (SERT) availability in OCD patients compared with healthy controls, supporting the hy–pothesis of a hyposerotonergic state in OCD. The current study focuses on the validation of the deer mouse (Peromyscus maniculatus bairdii) model of OCD and builds on previous work done in our laboratory. Deer mice that are bred and housed in confinement naturally develop two main forms of stereotypical behaviour, namely vertical jumping and pattern running. Furthermore, these behaviours can be catego–rized into various levels of severity, namely high (HSB), low (LSB) and non–stereotypic (NSB) cohorts. The seemingly purposeless and repetitive nature of these behaviours mimics the com–pulsions that characterize human OCD and constitutes the basis for the face validity of the model. However, although these two forms of stereotypy seem equally repetitive and persis–tent, stereotypical pattern runners do not complete the required number of cage revolutions per 30 minutes compared to the amount of jumps executed by stereotypical vertical jumpers. As only one set of criteria for the appraisal of the different topographies of deer mouse stereotypy has been applied in previous studies, the matter of whether pattern runners do in fact generate stereotypical behaviour of the same persistent and severe nature as opposed to the behaviour expressed by vertical jumpers, is problematic. Therefore, the first objective of the current study was to develop a new classification system for the appraisal of the different forms of behavioural topographies of deer mice and subse–quently to evaluate whether pattern runners can indeed be categorized into non–, low– and high stereotypical cohorts. After an eight–week behavioural assessment period, deer mice express–ing the two different behavioural topographies could be classified into non–, low– and high stereotypical cohorts (NSB, LSB, and HSB respectively), applying different criteria for each be–havioural topography. Based on the weekly mean stereotypy count generated during three 30–minute intervals of highest stereotypical behaviour over the course of a 12–hour assessment period, HSB pattern runners were found to execute on average 296 cage revolutions per 30 minutes, while HSB vertical jumpers executed an average of 3063 jumps per 30 minutes. This discrepancy between the generated numbers of the different topographies of stereotypy indi–cates that one classification system for the appraisal of both behavioural topographies is indeed inappropriate, and hence requires re–evaluation and validation. As patients with OCD present with a lower central SERT availability compared to healthy controls, the second objective of the study was to determine whether a decrease in SERT den–sity could be demonstrated in HSB animals compared to the NSB and LSB controls. After eight weeks of behavioural assessment, animals were sacrificed and frontal–cortical and striatal SERT binding was performed. HSB deer mice presented with significantly lower striatal, but not fron–tal–cortical SERT availability compared to the [NSB/LSB] control animals (p = 0.0009). As far as it concerns a lower SERT availability in HSB animals and involvement of the CSTC circuitry, this data is congruent with that demonstrated in human OCD and strengthens the construct validity of the model. Although previous studies undertaken in our laboratory demonstrated that deer mouse stereotypy is attenuated after chronic (21–day) fluoxetine administration, OCD only responds to chronic, but not sub–chronic treatment with the SSRIs. The lack of response of deer mouse stereotypy to sub–chronic treatment has not been established and therefore the third study ob–jective was to assess the behavioural effects of sub–chronic (7–day) and chronic (28–day) SSRI treatment on expression of deer mouse stereotypy. Chronic, but not sub–chronic treatment with oral escitalopram (50 mg/kg/day) significantly increased the number of intervals over a 12–hour assessment period during which no stereotypical behaviour were expressed by HSB deer mice (p = 0.0241) and decreased the number of intervals during which high–stereotypical be–haviour were executed (p = 0.0054). Neither chronic, nor sub–chronic treatment significantly affected the behaviour of animals in the [NSB/LSB] cohort. The fact that the model demon–strates a lack of response to sub–chronic treatment with high dose SSRIs, positively contributes to the predictive validity of the deer mouse model of OCD. The results from the current study therefore strengthens the construct and predictive valid–ity of the deer mouse model of OCD and confirm the model’s status as a prominent animal model of OCD. Not only is hyposerotonergic functioning in the CSTC circuitry implicated in the behaviour of HSB animals, but the model also demonstrates selective response to chronic SSRI–treatment - two core characteristics of human OCD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2012.

Obsessive–compulsive disorder (OCD) is a psychiatric condition that is characterized by two main symptom cohorts, namely recurrent inappropriate thoughts (obsessions) and seemingly purposeless repetitive motor actions (compulsions). In 70% of cases, the condition only re–sponds to chronic, but not sub–chronic, high dose treatment with the selective serotonin reup–take inhibitors (SSRIs), such as fluoxetine and escitalopram. This indicates a role for hyposero–tonergic functioning in the primary brain areas involved in OCD, namely the components of the cortico–striatal–thalamic–cortical (CSTC) circuit which include the prefrontal cortex, the basal ganglia, and the thalamus. A number of studies have demonstrated a lower serotonin trans–porter (SERT) availability in OCD patients compared with healthy controls, supporting the hy–pothesis of a hyposerotonergic state in OCD. The current study focuses on the validation of the deer mouse (Peromyscus maniculatus bairdii) model of OCD and builds on previous work done in our laboratory. Deer mice that are bred and housed in confinement naturally develop two main forms of stereotypical behaviour, namely vertical jumping and pattern running. Furthermore, these behaviours can be catego–rized into various levels of severity, namely high (HSB), low (LSB) and non–stereotypic (NSB) cohorts. The seemingly purposeless and repetitive nature of these behaviours mimics the com–pulsions that characterize human OCD and constitutes the basis for the face validity of the model. However, although these two forms of stereotypy seem equally repetitive and persis–tent, stereotypical pattern runners do not complete the required number of cage revolutions per 30 minutes compared to the amount of jumps executed by stereotypical vertical jumpers. As only one set of criteria for the appraisal of the different topographies of deer mouse stereotypy has been applied in previous studies, the matter of whether pattern runners do in fact generate stereotypical behaviour of the same persistent and severe nature as opposed to the behaviour expressed by vertical jumpers, is problematic. Therefore, the first objective of the current study was to develop a new classification system for the appraisal of the different forms of behavioural topographies of deer mice and subse–quently to evaluate whether pattern runners can indeed be categorized into non–, low– and high stereotypical cohorts. After an eight–week behavioural assessment period, deer mice express–ing the two different behavioural topographies could be classified into non–, low– and high stereotypical cohorts (NSB, LSB, and HSB respectively), applying different criteria for each be–havioural topography. Based on the weekly mean stereotypy count generated during three 30–minute intervals of highest stereotypical behaviour over the course of a 12–hour assessment period, HSB pattern runners were found to execute on average 296 cage revolutions per 30 minutes, while HSB vertical jumpers executed an average of 3063 jumps per 30 minutes. This discrepancy between the generated numbers of the different topographies of stereotypy indi–cates that one classification system for the appraisal of both behavioural topographies is indeed inappropriate, and hence requires re–evaluation and validation. As patients with OCD present with a lower central SERT availability compared to healthy controls, the second objective of the study was to determine whether a decrease in SERT den–sity could be demonstrated in HSB animals compared to the NSB and LSB controls. After eight weeks of behavioural assessment, animals were sacrificed and frontal–cortical and striatal SERT binding was performed. HSB deer mice presented with significantly lower striatal, but not fron–tal–cortical SERT availability compared to the [NSB/LSB] control animals (p = 0.0009). As far as it concerns a lower SERT availability in HSB animals and involvement of the CSTC circuitry, this data is congruent with that demonstrated in human OCD and strengthens the construct validity of the model. Although previous studies undertaken in our laboratory demonstrated that deer mouse stereotypy is attenuated after chronic (21–day) fluoxetine administration, OCD only responds to chronic, but not sub–chronic treatment with the SSRIs. The lack of response of deer mouse stereotypy to sub–chronic treatment has not been established and therefore the third study ob–jective was to assess the behavioural effects of sub–chronic (7–day) and chronic (28–day) SSRI treatment on expression of deer mouse stereotypy. Chronic, but not sub–chronic treatment with oral escitalopram (50 mg/kg/day) significantly increased the number of intervals over a 12–hour assessment period during which no stereotypical behaviour were expressed by HSB deer mice (p = 0.0241) and decreased the number of intervals during which high–stereotypical be–haviour were executed (p = 0.0054). Neither chronic, nor sub–chronic treatment significantly affected the behaviour of animals in the [NSB/LSB] cohort. The fact that the model demon–strates a lack of response to sub–chronic treatment with high dose SSRIs, positively contributes to the predictive validity of the deer mouse model of OCD. The results from the current study therefore strengthens the construct and predictive valid–ity of the deer mouse model of OCD and confirm the model’s status as a prominent animal model of OCD. Not only is hyposerotonergic functioning in the CSTC circuitry implicated in the behaviour of HSB animals, but the model also demonstrates selective response to chronic SSRI–treatment - two core characteristics of human OCD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2012.

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