Extensive research has been conducted demonstrating the utility of differential reinforcement as an effective intervention for self-injurious behavior. However, the majority of this literature requires teaching an alternative response to access reinforcement. Further evaluation of treating self-injurious behavior in individuals that already possess the repertories to contact reinforcement appropriately. Prior to initiating the study, functional assessments were completed for both participant that demonstrated high-rate bursts of mands served as a reliable precursor to self-injurious behavior. In the present study, we evaluated a waiting period and differential reinforcement of low rate behavior on reducing mands while keeping self-injurious behavior at or near zero levels. Results indicated that shorter waiting periods and DRL values were effective at reducing mands and maintaining near zero levels of self-injurious behavior.

區辨性增強低頻反應作業 (differential reinforcement of low-rate responding task, DRL task) 為一與時間相關聯之操作式制約行為作業，該作業常用於計時行為、行為抑制功能、或抗焦慮與抗憂鬱症等藥物之行為藥理研究的探討。雖然DRL作業是一種實驗室常用的動物行為模式，但是對於上述行為或藥理機制的探討往往缺乏一致性的解釋，其中可能的原因為DRL作業的行為同時包含了計時與行為抑制的成份。針對上述問題，本研究將以DRL行為作業為研究主題，探討作業習得歷程之神經機制。首先根據DRL作業之行為內涵，將作業的習得分為行為抑制與計時先後表現的兩個階段；並依據過去的研究文獻整理出的八個與行為抑制和計時表現相關之大腦區塊，以c-Fos免疫組織化學染色法探討行為抑制和計時的神經機制。實驗結果發現受試於行為抑制的表現階段，其眶眼皮質、內側前額葉皮質、與海馬CA1區域的c-Fos表現量較高；而在計時行為的表現階段，除了和行為抑制有關的三個大腦區塊外，尚有前扣帶迴、紋狀體、與齒狀迴呈現c-Fos表現量增加的現象。綜合以上結果，DRL-10秒作業於學習初期所進行的行為抑制可能和前額葉皮質與海馬體的神經互動有關；而學習較末階段的計時表現，則可能需要前額葉皮質、紋狀體、與海馬等三處較多的次級區域的組織加入，形成神經網路的方式支援之。 / Differential reinforcement of low-rate responding (DRL) task was an operant conditioned behavior based on temporal contingency. This task has been widely used to investigate the behavioral components of timing and behavioral inhibition, which is frequently used for pharmacological screening of anxiolytic and antidepressant drugs. Despite of being widely used as an animal behavioral model in the laboratory, but the performance of the DRL task was varied and inconsistent when the drug test conducted. One way to encounter this problematic issue is to differentiate the distinct behavioral components of DRL task and correlate the involved neural substrates, which was the theme investigated in the present study. This study first characterized the acquisition process of the DRL-10 sec task into behavioral inhibition and the timing stages, and then assessed the c-Fos levels by immunohistochemistry in the eight brain areas that potentially involved in behavioral inhibition and the timing processes. Regarding the stage of behavioral inhibition, significant increases in c-Fos-positive neurons were observed in the orbitofrontal cortex (OFC), the medial prefrontal cortex (mPFC), and the hippocampal CA1 area. At the stage of the timing being acquired, c-Fos immunohistochemical activity was highly expressed in the anterior cingulated cortex (ACC), OFC, mPFC, the dorsolateral striatum (dlS), the dentate gyrus (DG), and the hippocampal CA1 area. Together, these results showed that the functioning dual paths between the hippocampus CA1 and the prefrontal cortex (OFC and mPFC) are critically essential for developing the appropriate performance via behavioral inhibition in the early-stage of the DRL task and with three other areas (ACC, dlS, and DG) being recruited, an anatomical circuitry connecting prefrontal/striatal/hippocampal structures were involved in the acquisition of interval timing toward the later establishment of the DRL behavior.

Made available in DSpace on 2016-04-29T13:18:00Z (GMT). No. of bitstreams: 1 Dissertacao Thais Martins Sales.pdf: 1293785 bytes, checksum: 6161405c79ed51ec0c3dacacebe67ee1 (MD5) Previous issue date: 2006-05-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study was an attempt to investigate possible relations between responding that is reinforced according to schedules based on a temporal parameter and performing other activities to which no reinforcement contingencies are programmed. These activities have been called adjunctive behavior, collateral behavior or interim activities. Two questions guided this study: a) is there any difference in response rate, average time between reinforcers, and percentage of reinforced responses when an FI schedule or a DRL schedule is in force, if the subject can engage in other activities; b) are typical sequential patterns developed between responses when these schedules are in force? Four male food deprived rats were subjects of this experiment. The apparatus was an experimental box with seven chambers in which subjects could perform different activities, such as bar pressing, eating, running, drinking, and wood-chewing. For two subjects, bar pressing was reinforced according to three DRL schedules (DRL 4s, DRL 5s, and DRL 20s). One of the subjects was first kept in the chamber with the bar and food dispenser and then was allowed to access the other chambers, the other was first allowed to access the other chambers and then was kept in the chamber with the bar and food dispenser. For the other two subjects, bar presses were reinforced according to two FI schedules (FI 5s and FI 10s). One of the subjects first had access to all chambers and then was kept in the chamber with the bar and food dispenser, and the other was kept in the chamber with the bar and food dispenser during the whole experiment. Bar presses, reinforcement deliveries, and occupancy of chambers were recorded. Results show there was a difference in response rate, average time between reinforcers, and percentage of reinforced responses in both schedules, depending on the access condition, mainly when responses were reinforced according to schedules higher than FI 5s and DRL 4s. Higher response rates, lower average time between reinforcers and higher percentage of reinforced responses were observed for the DRL subjects when access was possible than when it was not possible, and higher response rates, higher average time between reinforcers and higher percentage of reinforced responses were observed for the FI subjects when access was possible than when it was not possible. No typical sequential patterns were observed when access was possible and either of the two studied schedules was in force. Results are discussed in terms of possible controlling variables to performing activities other than bar pressing when responding is being reinforced according to FI and DRL schedules / O presente trabalho é uma tentativa de investigação de possíveis relações entre o responder reforçado segundo dois esquemas de reforçamento que envolvem parâmetros temporais e o engajamento em atividades para as quais não há reforço programado, chamadas de atividades ínterim, comportamento adjuntivo ou comportamento colateral. Duas perguntas dirigiram a realização deste trabalho: a) há diferença na taxa de respostas, tempo médio entre reforços e porcentagem de respostas reforçadas segundo esquemas DRL e FI, caso haja possibilidade de engajamento em outras atividades? e b) alguma seqüência típica de engajamento em outras atividades é formada no intervalo entre respostas reforçadas segundo estes esquemas? Os sujeitos do experimento foram quatro ratos machos privados de alimento. Foi utilizada uma caixa experimental com sete compartimentos, nos quais era possível o engajamento em diferentes atividades: pressionar a barra, comer, beber, correr, roer madeira. Dois sujeitos tiveram as respostas de pressão à barra reforçadas segundo esquemas DRL com três valores diferentes (4s, 9s e 20s). Um deles passou, primeiro, por uma condição na qual o acesso a todos os compartimentos era permitido, chamada de aberta, e, segundo, por uma condição na qual era mantido no compartimento onde havia a barra e o comedouro, chamada de fechada, e o outro sujeito passou, primeiro, pela condição fechada e, segundo, pela condição aberta. Os outros dois sujeitos tiveram as respostas de pressão à barra reforçadas segundo esquemas FI com dois valores diferentes (5s, 10s). Um sujeito passou primeiro pela condição aberta e, depois, pela condição fechada e o outro passou apenas pela condição fechada. As pressões à barra, os reforços e a permanência nos compartimentos foram registrados. Os resultados mostraram que houve diferença na taxa de respostas, tempo médio entre reforços e porcentagem de respostas reforçadas em função da condição de acesso, especialmente quando as respostas de pressão à barra foram reforçadas segundo o esquema DRL 9s e DRL 20s, para os dois primeiros sujeitos, e segundo o FI 10s, para os outros dois sujeitos. Na condição aberta com esquema DRL em vigor, observou-se uma menor taxa de respostas, menor tempo entre reforços e maior porcentagem de respostas reforçadas do que na condição fechada, com o mesmo esquema em vigor. Na aberta com esquema FI em vigor, observou-se uma menor taxa de respostas, maior tempo entre reforços e maior porcentagem de respostas reforçadas do que na condição fechada, com o mesmo esquema em vigor. Seqüências típicas de engajamento em outras atividades não foram observadas quando o acesso era possível e o responder era reforçado segundo os esquemas FI e DRL. Os resultados são discutidos em termos de possíveis variáveis que controlam o engajamento em outras atividades, quando respostas são reforçadas segundo estes dois esquemas

Made available in DSpace on 2016-04-29T13:18:08Z (GMT). No. of bitstreams: 1 Livia Ferreira Godinho Aureliano.pdf: 559598 bytes, checksum: 8bc000da4999e46895b037747380a514 (MD5) Previous issue date: 2008-04-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study investigated the effects of duration exposure to activities without programmed reinforcers on performance under a temporal schedule of reinforcement. Two other questions guided this study: (a) Are there any changes in the patterns of activities that occur without programmed reinforcers dependent on the duration of exposure to these activities? (b) What would be the effect of the duration of this exposure over responding under a DRL schedule of reinforcement when subjects are placed in a standard operant chamber without access to other activities? Subjects were 4 male food deprived rats and 2 chambers were used: a standard operant chamber (1 compartment with lever and food recipient) and a 7 compartment chamber (activity chamber) in which subjects could engage on different activities: as bar pressing, eating, drinking, wood-chewing, and running. Bar presses were reinforced with food according to a DRL schedule that varied from 5 to 10 to 21s, but 2 subjects were exposed to this schedule on the standard chamber and the others on the activity chamber. Experimental sessions lasted 2 hours and bar presses, reinforce deliveries, and compartments visited were recorded. Results indicated performances in teach environment when DRL 10s or higher was in effect. On DRL 10s response and reinforcer rates and percentage of reinforced responses were higher, and time between reinforcements was lower for subjects on the standard chamber. In DRL 21s, however, these measures were reversed, suggesting that the availability of other activities could facilitate the acquisition and maintenance of performance on higher values DRL. There was indication of an increase on the percentage of reinforced bar pressing responses as a function of time of exposure to the experimental contingency in each session for all subjects. There were no significant differences on the percentages of reinforced responses of subjects on the standard or activity chamber box as a function of successive experimental sessions. However, percentages of reinforced responses were lower for subjects in the standard chamber at the beginning of the first sessions on each DRL value. Sequences of compartment visits, that seemed to be patterns were identified and the beginning of this patterns coincided with the increased effectiveness of the bar pressing responses. Results are discussed taking into account the differences between the criteria used in studies reported on the literature. The possible roles of the activities on the performance submitted on DRL schedules are also discussed / O presente estudo pretendeu investigar os efeitos do tempo de exposição dos sujeitos às atividades sem reforço programado sobre a efetividade do desempenho submetido a um esquema temporal de reforçamento. Duas outras perguntas nortearam o trabalho: (a) ocorreria alguma mudança nos padrões das atividades sem reforço programado em função do tempo de exposição a estas atividades? (b) qual o efeito do tempo de exposição aos diferentes valores do esquema DRL sobre o desempenho dos sujeitos na caixa padrão? Foram sujeitos 4 ratos machos, privados de alimento, que trabalharam em duas caixas experimentais, uma com 7 compartimentos nos quais havia a possibilidade de engajamento em atividades (pressionar a barra, comer, beber, roer madeira, correr na roda de atividades) e uma caixa operante padrão. As respostas de pressão à barra dos 4 sujeitos foram submetidas a um esquema DRL5s, 10 e 21s : 2 sujeitos foram expostos aos esquemas na caixa padrão e os outros dois na outra caixa. Todas as sessões experimentais tiveram a duração de 2 horas. Foram registradas as pressões à barra, os reforços obtidos e o tempo de permanência nos compartimentos. Os resultados indicaram que as maiores diferenças entre os desempenhos nos dois ambientes ocorreram a partir do DRL 10s, quando as taxas de respostas, de reforços e as porcentagens de respostas reforçadas foram maiores, e o tempo entre reforços foi menor para os sujeitos na caixa padrão. Em DRL 21s, no entanto, a situação se inverteu, sugerindo que a disponibilidade de outras atividades poderia facilitar a aquisição e adaptação do desempenho em valores mais altos do DRL. A análise dos efeitos do tempo de exposição à contingência em cada sessão sobre a efetividade da resposta de pressão à barra indicou que as porcentagens de respostas reforçadas aumentaram em função do tempo da sessão para os 4 sujeitos e não houve diferenças expressivas entre as porcentagens de respostas reforçadas ao longo das sessões experimentais. No entanto, para os sujeitos na caixa padrão, os percentuais alcançados no início das primeiras sessões em cada fase foram mais baixos do que para os sujeitos em ambiente aberto. Em relação ao padrão das atividades, uma seqüência de visita a compartimentos foi identificada e o início deste padrão coincidiu com o aumento da efetividade das respostas de pressão à barra. A discussão dos resultados leva em consideração as diferenças entre os critérios utilizados nos estudos relatados, além dos possíveis papéis das atividades sobre o desempenho submetido ao esquema de DRL

透過神經科學的研究，對於大腦的行為功能已有一定的認識，不同於以往的認識，目前認為神經行為機制不只由單一腦區或單一神經化學系統所調控。深部大腦電刺激經常被用來研究特定腦區的行為功能。但是，深部大腦電刺激的作用機制仍然不清楚。最近幾年臨床研究發現，利用電刺激在側韁核成功的治療憂鬱症患者。然而，目前認為側韁核與多巴胺系統互為負回饋作用，共同參與在動機行為的酬賞反應中。本實驗室先前的研究顯示，破壞韁核造成區辨性低頻操作式制約行為 (簡稱DRL行為)學習的障礙，然而，電刺激在側韁核造成DRL行為表現的結果還是未知的。所以，本實驗主要以電刺激在側韁核觀察大鼠行為上的改變，探討側韁核在行為上參與的功能。實驗一的結果顯示電刺激在側韁核並不影響自發性運動能力，在不同電流強度的刺激下也不會影響。實驗二的結果顯示電刺激在側韁核造成DRL 15秒的行為有類安非他命效果之行為表現，在高頻率電刺激有較顯著類安非他命的效果。實驗三的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響，會被多巴胺受體抑制劑所抵消，而單獨注射巴胺受體抑制劑並不影響DRL 15秒的行為。實驗四的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響，不會被正腎上腺素受體抑制劑所抵消。實驗五的結果顯示電刺激在側韁核造成DRL 72秒的行為之影響並不如DRL 15秒的行為顯著。實驗六的結果顯示電刺激在側韁核並不會造成大鼠無法區辨酬賞的量。綜合而言，側韁核在動機行為的角色，是透過影響多巴胺系統造成行為的改變。 / Behavioral function of the brain has been studied in neuroscience and progressively accumulated informative data to reveal the neurobehavioral mechanisms. It is now realized that those underlying mechanisms of behaviors is not as such simple as previous thought of limiting only in one locus of the brain or solely by one neurochemical system. The deep brain stimulation is usually used to study the behavioral function of specific brain regions. However, the mechanism of the deep brain stimulation is still unclear. The previous study has shown that electrical stimulation of the lateral habenula (LHb) successfully treated depression symptoms in the patients. It is proposed that an inhibitory role of LHb on the mibrain dopamine (DA) system which mediates the reward-related behavior. A previous study of this lab showed that lesion of habenula impaired the acquisition of differential reinforcement of low-rate responding (DRL) behavior. But, the effect of LHb stimulation on the DRL behavior is still unclear. To determine the functions of LHb involving in the behavior, the electrical stimulation was applied in LHb to observe the behavioral change of rats. The results of Experiment 1 showed that the LHb stimulation had no effect on locomotor activity. In Experiment 2, the LHb stimulation was shown to affect DRL 15-s behavior, which effects were similar to those affected by amphetamine. Experiment 3 showed that the DA receptor antagonists reversed the effects of LHb stimulation, while experiment 4 showed that norepinephrine (NE) receptor antagonists had no reversal effect on DRL 15-s behavior. In Experiment 5, the amphetamine-like behavior induced by LHb stimulation had subtle effects on DRL 72-s behavior. Experiment 6 showed that the LHb stimulation had no effect on a discrimination task. These data suggest that the LHb modulating DRL behavior is DA-dependent.