Thesis (Ph.D.)--University of Toledo, 2007. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Major advisor: Elizabeth Tietz. Includes abstract. Title from title page of PDF document. Bibliography: pages 88-94, 130-136, 178-189, 218-266.

Not available / text

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed Feb. 13, 2009). Includes bibliographical references.

Thesis--University of Oklahoma. / Bibliography: leaves 154-165.

Background: The incidence of neonatal opioid withdrawal syndrome (NOWS), a drug withdrawal syndrome mainly associated with opioid exposure in-utero has significantly increased in the United States over the last decade with infants with NOWS staying longer in the hospital than those without NOWS. Objectives: To determine if feeding tube use while on admission is associated with length of hospital stay among infants diagnosed with NOWS. We also compared the differences between infants with NOWS who required the use of feeding tubes while on admission, and those that did not, based on infant and maternal characteristics. Methods: This was a retrospective cohort study of infants delivered between July 1, 2011 and June 30, 2016 at Ballad Health System. Our inclusion criteria were infants who were exposed to opioids in-utero and received a diagnosis of NOWS based on 2 consecutive Finnegan scores of 10, or 3 consecutive scores of 8, or treatment with morphine. Medical chart record of 294 infants who met these criteria were reviewed for infant and maternal characteristics. Our outcome variable was infant length of hospital stay and our predictor variable was feeding tube use an indicator for feeding difficulties. Chi-square test and t-test were used to compare infant and maternal characteristics by feeding tube use. Simple linear regression models were used to assess the effect of feeding tube use and infant and maternal characteristics on infant length of hospital stay. Multiple linear regression was used to model infant length of hospital stay predicted by feeding tube use, while adjusting for neonatal intensive care unit (NICU) admission, treatment with morphine, and maternal benzodiazepine use during pregnancy. All analyses were done using SAS 9.4. Results: Of the 294 infants diagnosed with NOWS, 22.11% had feeding difficulties that necessitated use of feeding tubes. Infants who used feeding tubes were significantly more likely to be born preterm (20.31% vs 8.73%, p=0.0096) to be admitted into the NICU (98.46% vs 51.09%, p=

Con la finalidad de explorar con profundidad las bases neurobiológicas de la adicción a cannabinoides hemos llevado a cabo diferentes estudios farmacológicos y moleculares. El sustrato neuroanatómico de la dependencia física de cannabinoides ha sido investigado en ratones que recibieron un tratamiento crónico con el agonista WIN55,212-2. En este estudio, se observó que el cerebelo y en menor grado el hipocampo y la amígdala, participan en la manifestación comportamental del síndrome de abstinencia de cannabinoides. Estas tres áreas se caracterizan por presentar una alta densidad de receptores cannabinoides CB1. Además, hemos evaluado la participación de diversos sistemas de neurotransmisión como son los sistemas opioide y purinérgico endógenos, en las respuestas comportamentales inducidas tras la administración de cannabinoides. Especialmente, nos hemos interesado por aquellas respuestas que están estrechamente relacionadas con las propiedades adictivas de dichos compuestos, como son los efectos reforzantes y aversivos y el desarrollo de dependencia física. Para ello hemos utilizado ratones modificados genéticamente. El sistema opioide endógeno ha sido relacionado con la manifestación de las propiedades adictivas de los cannabinoides. En este trabajo, mediante la utilización de ratones dobles mutantes MOR/DOR, hemos demostrado que se requiere una acción cooperativa entre ambos tipos de receptores opioides para que el síndrome de abstinencia cannabinoide se exprese enteramente. Por otro lado, los ratones con una supresión del gen que codifica para el receptor de adenosina A2A no mostraron ni preferencia de plaza ni aversión de plaza condicionadas a la administración de THC. Además, estos ratones presentaron un síndrome de abstinencia de THC de menor severidad, lo que sugiere una participación específica de los receptores A2A en efectos de los cannabinoides relacionados con sus propiedades adictivas. Finalmente, teniendo en cuenta que el sistema cannabinoide parece estar implicado en la modulación de las propiedades adictivas de otras drogas de abuso como opiáceos, etanol, cocaína y MDMA, hemos investigado la posible implicación del sistema cannabinoide en las propiedades adictivas de la nicotina. Para ello, hemos evaluado las respuestas comportamentales inducidas tras la administración aguda y crónica de nicotina en ratones deficientes del receptor cannabinoide CB1. En este sentido, nuestro principal hallazgo ha sido que las propiedades gratificantes de la nicotina no se manifiestan en los ratones mutantes sin el receptor cannabinoide CB1. Este hecho resulta de especial interés para la búsqueda de nuevas alternativas terapéuticas que faciliten el abandono del hábito tabáquico. / Cannabinoid addiction includes complex neurobiological and behavioural processes. Recently, several animal models allowing the exploration of the neurobiological basis of cannabinoid addiction have been developed. Acute cannabinoid reinforcing effects play a major role in the initiation of cannabinoid addiction, whereas the negative consequences of drug abstinence have a crucial motivational significance for relapse and maintenance of the addictive process. To further explore the neurobiological basis of cannabinoid addiction, we have conducted several pharmacological and molecular studies. The neuroanatomical substrate of cannabinoid physical dependence has been investigated in mice chronically receiving the cannabinoid agonist WIN 55,212-2. Interestingly, the cerebellum and in a lesser extent the hippocampus and the amygdala are shown to participate in the behavioural expression of cannabinoid withdrawal. All these brain areas have a high density of CB1 cannabinoid receptors. Moreover, we have evaluated the involvement of various neurotransmitter systems, such as the purinergic and opioid systems, in the behavioural responses of cannabinoids related to their addictive properties, including rewarding effects and the development of physical dependence. For this purpose, we have used genetically modified mice. Mice lacking A2A adenosine receptors reveal lower motivational responses to cannabinoids and a decreased cannabinoid withdrawal syndrome, suggesting a specific involvement of these receptors in the addictive-related properties of cannabinoids. On the other hand, the opioid system has also been implicated in the addictive properties of cannabinoids. Here, by using double mutants for mu- and delta-opioid receptors, we show that a cooperative action of both receptors is required for the entire expression of cannabinoid dependence. Finally, taking into account that the cannabinoid system has been reported to participate in the addictive properties of other drugs of abuse, such as ethanol, cocaine and MDMA, we have investigated the possible role of the cannabinoid system in the addictive properties of nicotine. We have evaluated nicotine behavioural responses in mice lacking CB1 cannabinoid receptors. In this regard, our main findings are that some acute effects and motivational responses of nicotine can be modulated by the endogenous cannabinoid system which could be of interest in order to find new therapies to facilitate tobacco smoking cessation.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

O uso lesivo de bebidas alcoólicas é o terceiro maior fator mundial de risco de doenças e incapacitação. O álcool pode causar várias alterações no Sistema Nervoso Central (SNC), dentre elas, a diminuição do processamento de informações visuais. Alguns estudos avaliam as alterações nos processos perceptuais durante a Síndrome de Abstinência do Álcool (SAA) por meio da ilusão visual da máscara côncava. Essa ilusão exemplifica o fenômeno ilusório de inversão visual da profundidade de uma máscara humana oca, que é percebida como convexa. Foi encontrado um possível desequilíbrio entre os componentes bottom-up e top-down da percepção visual provocado pelo álcool, capaz de prejudicar a capacidade do indivíduo de perceber essa ilusão. Entretanto, a presente pesquisa investiga uma hipótese alternativa, e sugere que a redução na frequência de respostas de inversão pode resultar de mudanças de critérios para emitir as repostas e não em alterações perceptuais. Para isso, foram utilizados os parâmetros da Teoria da Detecção de Sinal (TDS) aplicada à psicofísica. Participaram da pesquisa 20 indivíduos saudáveis, 20 com SAA leve e 20 com SAA moderada. Eles realizaram duas tarefas experimentais de observação monocular dos lados côncavo e convexo, alternadamente, de uma máscara da face humana de tamanho reduzido. Na tarefa de confidence rating, foram julgadas a concavidade ou convexidade da máscara e o grau de certeza nas respostas, com certeza ou com dúvida. Na tarefa de escolha forçada entre duas alternativas (2AFC), as máscaras foram apresentadas aos pares alternados e o participante identificava o lado côncavo. A análise dos resultados revelou que os indivíduos com SAA moderada apresentaram maiores escores para os índices de sensibilidade R-index, Az, e da, na tarefa de confidence rating, apontando para uma capacidade significativamente maior de identificação e discriminação dos lados côncavo e convexo da máscara. Isto reflete um prejuízo significativo na capacidade destes indivíduos em perceber a ilusão da máscara côncava. Não houve diferença entre os grupos de indivíduos saudáveis e com SAA leve. Entretanto, os grupos com SAA apresentaram um maior grau de certeza em seus julgamentos comparativamente ao grupo controle. Resultados semelhantes para o grupo com SAA moderada foram encontrados na tarefa de escolha forçada para os índices d e taxa de acerto, indicando maior capacidade desses indivíduos em discriminar os dois lados da máscara. Todos os participantes apresentaram critérios de decisão moderados na tarefa de confidence rating. Os indivíduos saudáveis, na tarefa de escolha forçada, se mostraram tão capazes quanto os com SAA moderada na discriminação dos dois lados da máscara. Os indivíduos saudáveis, na tarefa de escolha forçada, se mostraram tão capazes quanto os com SAA moderada na discriminação dos dois lados da máscara. Entretanto, supõe-se que esses resultados foram provenientes de estratégias inesperadas por esses indivíduos em seus julgamentos, prejudicando a validade interna dos resultados; e representam um viés de pesquisa importante. As análises apontam para um possível desequilíbrio, já relatado em estudos anteriores, entre os componentes bottom-up e top-down da percepção visual, provocado pelo álcool, que impede o SNC de corrigir hipóteses perceptuais ambíguas. / The harmful use of alcoholic beverages is the third largest worldwide risk factor for illness and disability. Alcohol can cause several changes in the Central Nervous System (CNS), among them, the decrease in the processing of visual information. Some studies evaluate changes in perceptual processes during Alcohol Withdrawal Syndrome (AWS) through the hollow face illusion. Its exemplifies the illusory visual depth inversion of a hollow human mask, which is perceived as convex. A possible imbalance was found between the bottomup and top-down components of visual perception caused by alcohol, which could impair the individual\'s ability to perceive the illusion. However, the present research investigates an alternative hypothesis, and suggests that the reduction in the frequency of inversion responses may result from changes in the criteria to issue responses rather than on perceptual changes. The parameters of the Signal Detection Theory (SDT) applied to psychophysics allow this analysis. Twenty healthy subjects, 20 with mild AWS and 20 with moderate AWS participated in the study. They performed two experimental tasks of monocular observation of concave and convex sides, alternately, of a reduced size human face mask. In the task of confidence rating, the concavity or convexity of the mask and the degree of certainty in the answers were judged: certainly or with doubt. In the task of forced choice between two alternatives (2AFC), the masks were presented in alternating pairs and the participant identified the concave side. The analysis of the results revealed that individuals with moderate AWS presented higher scores for the sensitivity index scores R-index, Az, and da, pointing to a significantly greater capacity of identification and discrimination of the concave and convex sides of the mask. This reflects a significant impairment in the ability of these individuals to perceive the hollow face illusion. There was no difference between healthy individuals and with mild AWS. However, all groups with AWS presented a greater degree of certainty in their judgments compared to the control group. Similar results for the group with moderate AWS were found in the task of forced choice to the indices d and hit rate, indicating a greater ability of these individuals to discriminate both sides of the mask. Healthy subjects, on the task of forced choice, showed themselves to be as capable as those with moderate AWS in discriminating both sides of the mask. However, it supposed that these results were from unexpected strategies used by these individuals in their judgments, impairing the internal validity of the results, and represented an important research bias. The analyzes point to a possible imbalance, already reported in previous studies, between the bottom-up and top-down components of visual perception, caused by alcohol, which inhibits the CNS from correcting ambiguous perceptual hypotheses.

O uso lesivo de bebidas alcoólicas é o terceiro maior fator mundial de risco de doenças e incapacitação. O álcool pode causar várias alterações no Sistema Nervoso Central (SNC), dentre elas, a diminuição do processamento de informações visuais. Alguns estudos avaliam as alterações nos processos perceptuais durante a Síndrome de Abstinência do Álcool (SAA) por meio da ilusão visual da máscara côncava. Essa ilusão exemplifica o fenômeno ilusório de inversão visual da profundidade de uma máscara humana oca, que é percebida como convexa. Foi encontrado um possível desequilíbrio entre os componentes bottom-up e top-down da percepção visual provocado pelo álcool, capaz de prejudicar a capacidade do indivíduo de perceber essa ilusão. Entretanto, a presente pesquisa investiga uma hipótese alternativa, e sugere que a redução na frequência de respostas de inversão pode resultar de mudanças de critérios para emitir as repostas e não em alterações perceptuais. Para isso, foram utilizados os parâmetros da Teoria da Detecção de Sinal (TDS) aplicada à psicofísica. Participaram da pesquisa 20 indivíduos saudáveis, 20 com SAA leve e 20 com SAA moderada. Eles realizaram duas tarefas experimentais de observação monocular dos lados côncavo e convexo, alternadamente, de uma máscara da face humana de tamanho reduzido. Na tarefa de confidence rating, foram julgadas a concavidade ou convexidade da máscara e o grau de certeza nas respostas, com certeza ou com dúvida. Na tarefa de escolha forçada entre duas alternativas (2AFC), as máscaras foram apresentadas aos pares alternados e o participante identificava o lado côncavo. A análise dos resultados revelou que os indivíduos com SAA moderada apresentaram maiores escores para os índices de sensibilidade R-index, Az, e da, na tarefa de confidence rating, apontando para uma capacidade significativamente maior de identificação e discriminação dos lados côncavo e convexo da máscara. Isto reflete um prejuízo significativo na capacidade destes indivíduos em perceber a ilusão da máscara côncava. Não houve diferença entre os grupos de indivíduos saudáveis e com SAA leve. Entretanto, os grupos com SAA apresentaram um maior grau de certeza em seus julgamentos comparativamente ao grupo controle. Resultados semelhantes para o grupo com SAA moderada foram encontrados na tarefa de escolha forçada para os índices d e taxa de acerto, indicando maior capacidade desses indivíduos em discriminar os dois lados da máscara. Todos os participantes apresentaram critérios de decisão moderados na tarefa de confidence rating. Os indivíduos saudáveis, na tarefa de escolha forçada, se mostraram tão capazes quanto os com SAA moderada na discriminação dos dois lados da máscara. Os indivíduos saudáveis, na tarefa de escolha forçada, se mostraram tão capazes quanto os com SAA moderada na discriminação dos dois lados da máscara. Entretanto, supõe-se que esses resultados foram provenientes de estratégias inesperadas por esses indivíduos em seus julgamentos, prejudicando a validade interna dos resultados; e representam um viés de pesquisa importante. As análises apontam para um possível desequilíbrio, já relatado em estudos anteriores, entre os componentes bottom-up e top-down da percepção visual, provocado pelo álcool, que impede o SNC de corrigir hipóteses perceptuais ambíguas. / The harmful use of alcoholic beverages is the third largest worldwide risk factor for illness and disability. Alcohol can cause several changes in the Central Nervous System (CNS), among them, the decrease in the processing of visual information. Some studies evaluate changes in perceptual processes during Alcohol Withdrawal Syndrome (AWS) through the hollow face illusion. Its exemplifies the illusory visual depth inversion of a hollow human mask, which is perceived as convex. A possible imbalance was found between the bottomup and top-down components of visual perception caused by alcohol, which could impair the individual\'s ability to perceive the illusion. However, the present research investigates an alternative hypothesis, and suggests that the reduction in the frequency of inversion responses may result from changes in the criteria to issue responses rather than on perceptual changes. The parameters of the Signal Detection Theory (SDT) applied to psychophysics allow this analysis. Twenty healthy subjects, 20 with mild AWS and 20 with moderate AWS participated in the study. They performed two experimental tasks of monocular observation of concave and convex sides, alternately, of a reduced size human face mask. In the task of confidence rating, the concavity or convexity of the mask and the degree of certainty in the answers were judged: certainly or with doubt. In the task of forced choice between two alternatives (2AFC), the masks were presented in alternating pairs and the participant identified the concave side. The analysis of the results revealed that individuals with moderate AWS presented higher scores for the sensitivity index scores R-index, Az, and da, pointing to a significantly greater capacity of identification and discrimination of the concave and convex sides of the mask. This reflects a significant impairment in the ability of these individuals to perceive the hollow face illusion. There was no difference between healthy individuals and with mild AWS. However, all groups with AWS presented a greater degree of certainty in their judgments compared to the control group. Similar results for the group with moderate AWS were found in the task of forced choice to the indices d and hit rate, indicating a greater ability of these individuals to discriminate both sides of the mask. Healthy subjects, on the task of forced choice, showed themselves to be as capable as those with moderate AWS in discriminating both sides of the mask. However, it supposed that these results were from unexpected strategies used by these individuals in their judgments, impairing the internal validity of the results, and represented an important research bias. The analyzes point to a possible imbalance, already reported in previous studies, between the bottom-up and top-down components of visual perception, caused by alcohol, which inhibits the CNS from correcting ambiguous perceptual hypotheses.