Previous research has indicated two distinctive characteristics of flavour-aversion learning in rats: (1) rats very readily associate flavors with an internal malaise (toxicosis) , as evidenced by their subsequent aversion to the flavor, but they do not readily associate flafors with peripherally-applied electric shock. In contrast, rats readily associate auditory and visual stimuli with shock but not with toxicosis; (2) rats associate flavors with a subsequent toxicosis even when the gustatory stimulus is removed hours prior to onset of toxicosis. However, associations are formed between audio/visual cues and shock only if the offset of the signal does not precede onset of shock by more than one or two minutes. It has been suggested that the unique features of flavour-aversionn learning result from the fact that toxicosis is primarily a visceral experience while shock is applied to somesthetic receptors. However, toxicosis differs from shock along a number of dimensions in addition to receptor site. Most notably, toxicosis typically rises to a peak intensity over a period of many minutes and lasts for hours while shock is usually applied with a rapid onset (milliseconds) and short duration (seconds or milliseconds). Inasmuch as aversion learning experiments have confounded the receptor site of the aversive stimulus with its distinctive temporal features, it is not clear whether receptor site or temporal features is the functionally important characteristic of toxicosis as an aversive stimulus in the taste-aversion learning preparation. To determine the role played by the temporal features of the aversive stimulus in taste-aversion learning, rats were prepared with a stomach balloon and stomach balloon inflation was paired with ingestion of a flavored solution. In contrast to toxicosis, the onset/offset rate and duration of balloon inflation may be directly manipulated thus permitting application of a relatively discrete internal stimulus (in comparison to toxicosis) to visceral receptors. Experiments presented here found: (a) rats associated a flavor with a stomach balloon inflation as indicated by an aversion to the flavor during a two-solution preference test. In contrast to toxicosis, the stomach balloon inflation had a rapid onset (seconds) and short duration (minutes). Control groups demonstrated that the rapid onset, short duration balloon inflation did not produce the long lasting malaise characteristic of toxicosis. (b) Rats associated a flavor with a rapid onset, short duration balloon inflation even when exposure to the flavor was terminated many minutes prior to onset of balloon inflation. (c) Rats readily associated a flavor with balloon inflation but not with shock, and an auditory stimulus with shock but not with balloon inflation, even though balloon inflation and shock were equated in terms of their temporal parameters. These findings clearly indicate that the very slow onset and long duration characteristics of toxicosis are not the functionally important features of toxicosis as the aversive stimulus in the taste-aversion learning preparation. Furthermore, the unique temporal features of toxicosis and shock do not appear responsible for the distinctive characteristics of flavor-aversion learning in rats. / Thesis / Doctor of Philosophy (PhD)

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Introdução: O ato da micção é processo complexo que envolve o encéfalo, a medula espinhal, o sistema nervoso periférico e a integridade neuromuscular do trato urinário baixo. Essa integridade permite a ocorrência da fase de armazenamento de urina na bexiga e, a seguir, da fase de esvaziamento vesical. Havendo comprometimento das conexões entre esses componentes, tanto o enchimento quanto o esvaziamento vesical podem estar comprometidos. Conhecendo as propriedades do extensômetro elétrico de resistência, foi proposta a construção de um aparato com capacidade de avaliar a condição de enchimento vesical e que permita a correlação direta com a pressão intravesical. Objetivo: Desenvolver e demonstrar o funcionamento de um equipamento para monitoramento contínuo da tensão do detrusor, em coelhos, durante a fase de enchimento vesical. Material e Métodos: Foram utilizadas 12 coelhas da raça Nova Zelândia. Após anestesia, a bexiga foi exposta por incisão mediana e a uretra foi obstruída com ligadura por fio de algodão. O sensor de tensão foi suturado ao detrusor e confeccionada cistostomia por punção com Abocath 16, utilizada para enchimento e esvaziamento vesical e cistometria, avaliada pelo equipamento Dynamed® - modelo Dynapack MPX-B16. Os coelhos foram submetidos ao procedimento de monitorização inicial (enchimento vesical monitorado pela cistometria) e a medida da tensão da parede vesical - com a bexiga totalmente preservada. Resultados: No decorrer dos experimentos e com a conclusão das análises estatísticas, encontramos uma correlação muito importante entre os dados. Quando se coloca em foco apenas um animal, verifica-se uma grande correlação entre os dados provenientes do volume infundido na bexiga em função da curva gerada para a pressão intravesical que, por sua vez, acompanha fidedignamente a curva da tensão lida na parede vesical do mesmo animal. Quando avaliados conjuntamente, verificasse que os dados são muito próximos uns dos outros, tais como o volume infundido e a tensão final em mV, lida pelo equipamento desenvolvido. Conclusão: O equipamento foi desenvolvido e, com base nos resultados obtidos, mostrou-se adequado para o monitoramento contínuo da tensão vesical do detrusor e sua correlação com o volume vesical, em coelhos, durante a fase de enchimento vesical. / Introduction: Urination is a complex process which involves the brain, the spinal cord, the peripheral nervous system and the neuromuscular integrity of the lower urinary tract. It is the unimpaired condition of all those parts that allows the bladder to go through its functional states - storage phase (filling) and voiding phase (emptying). Problems within these anatomical structures connections can also compromise both phases. This thesis presents the design of a new device which uses an electrical resistance strain gauge to evaluate the bladder\'s filling and its direct correlation with the intravesical pressure. Objective: To develop and demonstrate the operation of a new device that checks continuously rabbit\'s detrusor pressure during bladder filling. Material and Methods: 12 rabbits of New Zealand race were used. After anesthesia, their bladders and urethras were exposed via an abdominal incision made at the midline. Then, the urethra obstruction was performed by ligation using cotton thread. The tension sensor was sutured to the detrusor and a cystostomy puncture was made with an Abocath 16. The puncture was used for filling and voiding cystometry using the urodynamic equipment, Dynamed - Dynapack model MPX-B16. Data collected by this equipment was used as the baseline. Rabbits underwent an initial monitoring procedure, bladder\'s filling cystometry using the Dynamed equipment, and voltage measurement of the bladder wall using the new device - bladder integrity was preserved. Results: During the experimental phase, completion of the statistical analyzes showed us a very significant data correlation. Correlation was stronger when evaluating each animal data individually. The infused volume in the bladder, which was verified by the intravesical pressure curve, and the voltage measured on the bladder wall faithfully followed each other. When evaluating the combined data of all rabbits, correlation was less but still significant. Volume and voltage curves still resembled one another, especially the infused volume with the final voltage reading, in mV. Conclusion - Based on the results of the experimental phase in animals, the developed device is adequate for continuous detrusor pressure monitoring and its correlation with the bladder volume in the storage phase.

Introdução: O ato da micção é processo complexo que envolve o encéfalo, a medula espinhal, o sistema nervoso periférico e a integridade neuromuscular do trato urinário baixo. Essa integridade permite a ocorrência da fase de armazenamento de urina na bexiga e, a seguir, da fase de esvaziamento vesical. Havendo comprometimento das conexões entre esses componentes, tanto o enchimento quanto o esvaziamento vesical podem estar comprometidos. Conhecendo as propriedades do extensômetro elétrico de resistência, foi proposta a construção de um aparato com capacidade de avaliar a condição de enchimento vesical e que permita a correlação direta com a pressão intravesical. Objetivo: Desenvolver e demonstrar o funcionamento de um equipamento para monitoramento contínuo da tensão do detrusor, em coelhos, durante a fase de enchimento vesical. Material e Métodos: Foram utilizadas 12 coelhas da raça Nova Zelândia. Após anestesia, a bexiga foi exposta por incisão mediana e a uretra foi obstruída com ligadura por fio de algodão. O sensor de tensão foi suturado ao detrusor e confeccionada cistostomia por punção com Abocath 16, utilizada para enchimento e esvaziamento vesical e cistometria, avaliada pelo equipamento Dynamed® - modelo Dynapack MPX-B16. Os coelhos foram submetidos ao procedimento de monitorização inicial (enchimento vesical monitorado pela cistometria) e a medida da tensão da parede vesical - com a bexiga totalmente preservada. Resultados: No decorrer dos experimentos e com a conclusão das análises estatísticas, encontramos uma correlação muito importante entre os dados. Quando se coloca em foco apenas um animal, verifica-se uma grande correlação entre os dados provenientes do volume infundido na bexiga em função da curva gerada para a pressão intravesical que, por sua vez, acompanha fidedignamente a curva da tensão lida na parede vesical do mesmo animal. Quando avaliados conjuntamente, verificasse que os dados são muito próximos uns dos outros, tais como o volume infundido e a tensão final em mV, lida pelo equipamento desenvolvido. Conclusão: O equipamento foi desenvolvido e, com base nos resultados obtidos, mostrou-se adequado para o monitoramento contínuo da tensão vesical do detrusor e sua correlação com o volume vesical, em coelhos, durante a fase de enchimento vesical. / Introduction: Urination is a complex process which involves the brain, the spinal cord, the peripheral nervous system and the neuromuscular integrity of the lower urinary tract. It is the unimpaired condition of all those parts that allows the bladder to go through its functional states - storage phase (filling) and voiding phase (emptying). Problems within these anatomical structures connections can also compromise both phases. This thesis presents the design of a new device which uses an electrical resistance strain gauge to evaluate the bladder\'s filling and its direct correlation with the intravesical pressure. Objective: To develop and demonstrate the operation of a new device that checks continuously rabbit\'s detrusor pressure during bladder filling. Material and Methods: 12 rabbits of New Zealand race were used. After anesthesia, their bladders and urethras were exposed via an abdominal incision made at the midline. Then, the urethra obstruction was performed by ligation using cotton thread. The tension sensor was sutured to the detrusor and a cystostomy puncture was made with an Abocath 16. The puncture was used for filling and voiding cystometry using the urodynamic equipment, Dynamed - Dynapack model MPX-B16. Data collected by this equipment was used as the baseline. Rabbits underwent an initial monitoring procedure, bladder\'s filling cystometry using the Dynamed equipment, and voltage measurement of the bladder wall using the new device - bladder integrity was preserved. Results: During the experimental phase, completion of the statistical analyzes showed us a very significant data correlation. Correlation was stronger when evaluating each animal data individually. The infused volume in the bladder, which was verified by the intravesical pressure curve, and the voltage measured on the bladder wall faithfully followed each other. When evaluating the combined data of all rabbits, correlation was less but still significant. Volume and voltage curves still resembled one another, especially the infused volume with the final voltage reading, in mV. Conclusion - Based on the results of the experimental phase in animals, the developed device is adequate for continuous detrusor pressure monitoring and its correlation with the bladder volume in the storage phase.

<p>Increased visceral pain is often seen in patients with gastrointestinal (GI) inflammation. Some studies, however, have suggested that such pain may persist after resolution of damage or inflammation. Despite the debilitating pain associated with GI inflammation, and its significant impact on affected individuals, few studies have addressed this issue. We hypothesized that altered visceral pain responses would persist after resolution of a bout of colitis in an animal model of colitis. We studied the pain responses to colorectal distention in Wistar rats with dinitrobenzene sulfonic acid (DNBS)-induced colitis, using changes in heart rate as an index of pain. Colonic inflammation had resolved by day 15 after DNBS administration. The assessment of colonic inflammation was based on histological scores, colonic tissue pro-inflammatory cytokine levels and myleoperoxidase activity. Rats examined at 15 days post-DNBS administration exhibited diminished pain responses to colorectal distention as compared to healthy rats. This was associated with significant increases in colonic tissue levels of IL-4 and IL-10 as compared to healthy rats, indicating a possible role for these anti-inflammatory cytokines in counteracting the generation of pain and hyperalgesia. We also studied the effects of hydrogen sulfide (H2S) in our animal model, by administering inhibitors of two of the key enzymes involved in the production of H2S. Our results demonstrated that inhibition of H2S production did not significantly alter the pain responses observed in rats at 15 days post-DNBS administration. In summary, our results demonstrate altered autonomic responses to colorectal distension following resolution of colitis. Further research on the role of anti-inflammatory cytokines and H2S may help to determine the mechanism underlying this effect.</p> / Master of Science (MSc)