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.

Made available in DSpace on 2016-06-02T20:30:07Z (GMT). No. of bitstreams: 1 4749.pdf: 4117281 bytes, checksum: 6047b5a8a4c0428901b24875ac28c98a (MD5) Previous issue date: 2012-07-05 / Universidade Federal de Minas Gerais / Stimulus equivalence literature has shown robust data, but with some result variability between participants, with some forming classes promptly and others who do not demonstrate the expected class formation. Matching to sample (MTS) is the commonly used procedure to verify these relationships formation. However, a situation involving experimental MTS is rather complex regarding the number of potential relationships, so that the participant can form classes based on different equivalence relations that those manipulated by the experimenter. For example, responses that are counted as instances of the same relationship may include different control topographies, some responses controlled by relations of selection (when control of the participant's response is given "selecting" the correct stimulus in the presence of a particular model) while others are controlled by rejection (when there is a "rejection" of a incorrect stimulus in the presence of a particular model). One possibility to check and monitor the different control relations during the baseline training is to use special procedures to induce and identify it. One of these procedures is the blank procedure in which a black square is gradually introduced over attempts conditional discrimination baseline so as to occlude participant s sight of it. This way, separately topographies of selection and rejection can be checked, as well as differences in the formation of equivalence relations. AB, BC and CD relations trainings were programmed, each set with three different stimuli (eg: A1, A2 and A3; B1, B2 and B3, etc.). Control only for rejection or only by selection in baseline training conditional relations BC were planned in one of the trainings, and results compared with another training in which all relations were taught either by selection or by rejection. Other parametric variations (nodal distance increase and extensive pre-training role in positive equivalence results using the mask) were also investigated to advance understanding of the variables that may be related to the equivalence formation. The results indicate that learning BC relationship with only one control relation is not sufficient for the equivalence classes ready formation. These are not guaranteed even if only selecting topographies are learned. Have the whole training - ensuring that the participant learns the relations either by rejection or by selection - assures equivalence formation in much more training opportunities. The results indicated that the extensive pre-training was useful to install some prerequisites behaviors required in the task pairing. Participants who passed the pre-training before starting the experiment were partially successful in achieving the criteria for baseline conditional relations learning training, but the generalized conditional responding did not occur as readily as expected, although it seems to have occurred faster for participants who had gone through extensive pre-training. / A literatura de equivalência de estímulos tem mostrado dados robustos, porém com certa variabilidade de resultados entre participantes, com alguns formando classes prontamente e outros que não demonstram formação das classes esperadas. O emparelhamento com o modelo (MTS) é o procedimento comumente usado para verificar a formação dessas relações, no entanto uma situação experimental envolvendo MTS é bastante complexa quanto ao número de relações potenciais, de tal modo que o participante pode formar equivalências com base em relações diferentes das que são definidas pelo experimentador. Por exemplo, as respostas que são computadas como instâncias de uma mesma relação podem incluir diferentes topografias de controle, sendo algumas respostas controladas por relações de seleção (quando o controle da resposta do participante é dado pelo selecionar o estímulo correto diante de um determinado modelo) enquanto outras são controladas por rejeição (quando há a rejeição de um estímulo incorreto na presença de um determinado modelo). Uma possibilidade de verificar e controlar as diferentes relações de controle durante a linha de base é utilizar procedimentos especiais para induzir e identificar estas relações. Um desses procedimentos é o procedimento de máscaras, em que um quadrado negro é introduzido gradualmente ao longo de tentativas de discriminação condicional de linha de base, de modo a obliterar a visão do estímulo por parte do participante. Assim é possível verificar separadamente as topografias de seleção e de rejeição, bem como as diferenças nas formações de relações de equivalência. Foram programados treinos das relações AB, BC e CD, sendo que cada conjunto apresentava três estímulos diferentes (por exemplo: A1, A2 e A3; B1, B2 e B3 etc.), induzindo o controle apenas por rejeição ou apenas por seleção no treino de relações condicionais de linha de base da relação BC, em um dos treinos, e comparando-o com outro treino em que todas as relações eram ensinadas tanto por seleção quanto por rejeição. Outras variações paramétricas (aumento da distância nodal e papel do pré-treino extensivo nos resultados positivos para equivalência em treinos lineares com uso da máscara) também foram investigadas para avançar na compreensão das variáveis que podem estar relacionadas à formação de equivalência. Os resultados indicam que a aprendizagem da relação BC com apenas uma das relações de controle não é suficiente para a pronta formação de classes de equivalência, mesmo que sejam garantidas apenas relações controladas por seleção do S+. Já o treino completo - assegurando que o participante aprenda as relações tanto por rejeição quanto por seleção - garantiu a formação de equivalência em muito mais oportunidades que os outros treinos. Os resultados indicaram que o pré-treino extensivo foi útil em instalar alguns comportamentos pré-requisitos requeridos na tarefa de emparelhamento, na medida em que os participantes que passaram pelo pré treino antes de iniciar o experimento obtiveram sucesso parcial em alcançar os critérios de aprendizagem durante o treino das relações condicionais de linha de base, mas o responder condicional generalizado não ocorreu tão prontamente quanto o esperado, embora pareça ter ocorrido mais rapidamente para os participantes que haviam passado pelo pré-treino extensivo.

Made available in DSpace on 2016-06-02T19:46:02Z (GMT). No. of bitstreams: 1 2192.pdf: 1839438 bytes, checksum: c33118a6f61ebb96b4cadfa58a00b102 (MD5) Previous issue date: 2008-02-28 / Universidade Federal de Minas Gerais / The stimulus equivalence concept has been used by behavior analysts as an instrument to systematic verifications of new and complex repertories, offering an operational specification of symbolic behavior and distinguishing between two kinds of relational stimulus pairs: conditional relations and equivalence relations. The most often used procedure to verify emergence of equivalence relations is the matching to sample (MTS), in which two conditional relations between stimulus pairs are taught. In this procedure the experimenter does not know the baseline stimulus control topographies and the subject answers, although could be similar to those expected, may include different control topographies, being some controlled by selection and others controlled by rejection. One alternative possibility to verify different baseline control relations is the use of special procedures to induce and identify these relations, like the blank comparison procedure. In this procedure, a black square is introduced on the baseline conditional discrimination trials to block the stimulus for the subject. The present study used the blank comparison procedure with seven normally developing children with school failure history, to separated verify the selection and rejection topographies and the differences in the emergence of equivalence relations. Different arbitrary visual stimulus sets were used in each training: conditional discriminations with both selection and rejection topographies, conditional discriminations only with rejection topographies in the BC relations, and conditional discriminations only with selection topographies in the BC relations. The blank comparison procedure was used to generate these controls on the baseline conditional discriminations. All participants met high percents of correct answers after the training with both control topographies and demonstrating equivalence, although some children needed other procedures to remediate fails in the training. After the trainings with only rejection or selection control in the BC relations, no children obtain a positive equivalence test outcome, pointing that guarantee of both rejection and selection control topographies could minor the emergent relations test outcomes variability in the matching to sample procedures. / O conceito de equivalência de estímulos tem sido usado por analistas do comportamento como instrumento para verificar sistematicamente repertórios novos e complexos, oferecendo uma especificação operacional para o comportamento simbólico, distinguindo dois tipos de relações entre pares de estímulos: relações condicionais e relações de equivalência. O procedimento mais comumente usado para verificar a geração de relações de equivalência é o emparelhamento com o modelo (matching to sample), em que são ensinadas relações condicionais entre pares de estímulos, verificando-se a emergência de relações de equivalência. Porém, neste procedimento o experimentador desconhece as topografias de controle de estímulos da linha de base, já que as respostas, embora aparentemente similares, podem ocorrer sob controle de diferentes topografias, sendo algumas delas controladas por relações de seleção enquanto outras são controladas por rejeição. Uma alternativa para verificar e controlar as diferentes relações de controle na linha de base é utilizar procedimentos especiais para induzir e identificar estas relações, como o procedimento de máscaras. Neste procedimento, um quadrado negro é introduzido nas tentativas de discriminação condicional de linha de base, de modo a obliterar a visão de um dos estímulos por parte do participante. O presente estudo utilizou o procedimento de máscaras com sete crianças com desenvolvimento típico e histórico de fracasso escolar, verificando separadamente as topografias de seleção e de rejeição, bem como as diferenças nas formações de relações de equivalência. Para isso, foram usados conjuntos diferentes de estímulos visuais arbitrários em cada treino, comparando os resultados de sondas de relações emergentes para cada participante sob diferentes condições: treinos de relações condicionais tanto por rejeição, quanto por seleção; somente por rejeição; e somente por seleção. O procedimento de máscaras foi utilizado para induzir topografias de controle de estímulo por rejeição e por seleção nas discriminações condicionais de linha de base. Todos os participantes alcançaram porcentagens altas de acertos nas relações testadas após o treino em que foram usadas ambas as topografias de controle, demonstrando equivalência, embora alguns participantes tenham necessitado de procedimentos remediativos. No entanto, depois dos treinos apenas por rejeição ou apenas por seleção, nenhuma criança demonstrou equivalência e os desempenhos nas tentativas de linha de base intercaladas com as sondas de relações emergentes tornou-se menos acurado. Garantir o controle do responder tanto por seleção do S+ quanto por rejeição do S- pode diminuir a variabilidade dos resultados obtidos nas sondas de relações emergentes em procedimentos de emparelhamento com o modelo.