Thesis (M.S.W.)--University of Hong Kong, 1994. / Includes bibliographical references (leaves 116-120).

Thesis (M.A.)--Lancaster Bible College, 2005. / Abstract. Includes bibliographical references (leaves 65-68).

Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve certo grau de estresse) durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. Após estes primeiros experimentos procuramos verificar também a capacidade do exercício físico em reverter o prejuízo da memória causado pela separação maternal, procedimento que causa um déficit de memória já descrito pela literatura, utilizando, também, o teste de esquiva inibitória. O estresse diário realçou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo de memória curta (MCD) e de longa duração (MLD) na tarefa do reconhecimento em 2 semanas mas somente de MCD após 8 semanas; e não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício realçou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou MCD e MLD na tarefa do reconhecimento após 2 mas não após 8 semanas; e realçou uma medida importante da aprendizagem espacial após 8 semanas (latência de escape), mas não outras medidas. Em relação ao grupo de animais que foram submetidos à separação maternal verificou-se que o exercício crônico foi capaz de reverter o déficit da MCD e MLD na esquiva inibitória e da MCD no reconhecimento de objetos, mas não teve efeitos sobre o prejuízo da MLD nesta tarefa e sobre a memória espacial testada no Labirinto Aquático de Morris. Portanto, o exercício físico crônico tem uma influência positiva sobre amemória e, adicionalmente, pode ser visto como uma ferramenta terapêutica para reverter determinados déficits de memória. / Here we studied the effects of daily forced exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests were: habituation of exploration in an open field, object recognition and spatial memory in Morris water maze. After these experiments we also tried to verify the physical exercise capacity to revert the memory deficit caused by maternal deprivation, procedure that causes a memory deficit already reported, by means of the inhibitory avoidance test. Daily footshock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task after 2 weeks but only STM after 8 weeks; and had no effect on the spatial task after neither 2 or 8 weeks. The exercise protocol also enhanced habituation in the open field after 2 but not 8 weeks; it hindered STM and LTM in the recognition task after 2 but not at 8 weeks; and it enhanced one important measure of spatial learning after 8 weeks (latency to escape) but not other measures. In relation of the animals that was submitted to maternal deprivation we verified that the exercise is capable to revert the deficit of STM and LTM in inhibitory avoidance test and of STM in object recognition test, but don’t have any effect on the prejudice of LTM in object recognition and in spatial memory verify using the Morris water maze test. Thus, the physical exercise had a positive influence on memory and, additionally, it can be seen like one therapeutic strategy to reverts some memory deficits.

Dor em pediatria tem sido o foco de muitos estudos nas últimas décadas devido ao fato de que neonatos apresentam menor limiar a estímulos nocivos e inócuos em relação aos adultos. Desta forma, o uso de analgésicos é frequente para sedação e analgesia em UTIs pediátricas, e entre os opioides, a morfina é um dos mais utilizados. Adicionalmente, exposição a estímulos estressantes como a deprivação materna está entre os fatores ambientais relacionados a alterações no desenvolvimento neural. O estresse social ou a negligência do cuidado parental, e mais precisamente do cuidado materno em ratos, está associado a importantes alterações comportamentais na vida adulta. Entre estas alterações apresentadas ao longo da vida estão alterações na resposta ao estresse, e à alteração na sensibilidade a estímulos dolorosos, indexadas por hiperalgesia. Consquentemente, o estresse social gerado pela deprivação materna está relacionado a prejuízos cognitivos, emocionais e sociais, além de alterações neuroquímicas de longo prazo. Deste modo, é necessário atenção, prevenção e tratamento a esses eventos físicos, emocionais e comportamentais no período neonatal e durante a infância, uma vez que as bases neurobiológicas envolvidas nestes fenômenos ainda não foram completamente elucidadas. Considerando a relevância do tema, o objetivo deste estudo foi verificar os efeitos do tratamento com 5 μg de morfina, uma vez ao dia, do P8 ao P14 e a exposição a deprivação materna por 3 horas durante os primeiros 10 dias de vida em curto (P16), médio (P30) e longo prazo (P60), sobre o desenvolvimento dos reflexos neuromotores da prole por meio do Reflexo de Endireitamento, Geotaxia Negativa e Marcha; comportamento nociceptivo por meio dos testes Tail-Flick e Placa Quente, respectivamente. Um total de 58 filhotes foi utilizado. Os animais foram divididos em 5 grupos: controle total (C), que não recebeu nenhuma intervenção; salina (S), que recebeu solução salina; morfina (M), que recebeu morfina; deprivado salina (DS), que foram submetidos a deprivação maternal e receberam solução salina; e deprivado morfina (DM), que foram submetidos a deprivação maternal e receberam morfina. Em relação aos testes neuroquímicos, foram analisados níveis de BDNF, NGF, IL-1β e IL-4 em tronco e córtex cerebral que estão relacionados a fenômenos modulatórios em sistemas nervoso e imune. Os animais que receberam morfina e os deprivados maternos que receberam morfina apresentaram atraso no desenvolvimento dos reflexos iniciais. Alterações neuroquímicas também foram observadas. Os níveis de BDNF no tronco encefálico foram diminuídos em animais que receberam morfina e deprivação materna. Animais deprivados apresentaram um aumento nos níveis de NGF no tronco encefálico. Além disso, observou-se um aumento nos níveis de NGF do córtex cerebral em animais que receberam morfina, deprivados maternos e deprivados maternos que receberam morfina. Uma diminuição no limiar nociceptivo foi observada em animais que receberam morfina, deprivados maternos e os deprivados maternos que receberam morfina. Também houve interações em tronco encefálico e córtex cerebral nos níveis de BDNF, IL-1β e IL-4 entre as variáveis independentes: tratamento, deprivação e tempo, o que levou à modificação nos níveis centrais dos neuroimunomoduladores avaliados. Estes dados demonstram a importância de estudos focados nos efeitos do tratamento com morfina no período neonatal ao longo da vida, assim como na busca por alternativas terapêuticas que possam reverter possíveis alterações decorrentes da separação materna no período neonatal. / Pediatric pain has been the focus of many studies in the last decades due to the fact that neonates have a lower threshold for innocuous and noxious stimuli than for adults. Thus, the use of analgesics is frequent for sedation and analgesia in pediatric intensive care units, and among opioids, morphine is one of the most used. Additionally, exposure to stressful stimuli such as maternal deprivation is among the environmental factors related to changes in neural development. The social stress or neglect of parental care, and more precisely maternal care in rats, is associated with important behavioral changes in adult life. Among these changes presented throughout life are changes in the response to stress, and the change in sensitivity to painful stimuli, indexed by hyperalgesia. Consequently, the social stress generated by maternal deprivation is related to cognitive, emotional and social impairments, further to long-term neurochemical changes. Thus, attention, prevention and treatment are necessary to these physical, emotional and behavioral events in the neonatal period and during childhood, since the neurobiological bases involved in these phenomena have not yet been fully elucidated. Considering the relevance of the subject, the objective of this study was to verify the effects of treatment with 5 μg of morphine once a day from P8 to P14 and exposure to maternal deprivation for 3 hours during the first 10 days of short (P16), medium (P30) and long- term (P60), on the development of neuromotor reflexes of offspring through the righting Reflex, Negative Geotaxis and Gait; nociceptive behavior through the Tail-Flick and Hot Plate tests, respectively. A total of 58 puppies were utilized. The animals were divided in 5 groups: the total control group (C), which did not receive any intervention; saline group (S), which receive saline solution; morphine group (M), which receive morphine; deprived saline (DS), which were subjected to maternal deprivation and receive saline solution; and deprived morphine group (DM), which were subjected to maternal deprivation and receive morphine. In relation to the neurochemical tests, levels of BDNF, NGF, IL-1β and IL-4 were analyzed in the brainsteam and cerebral cortex and are related to modulatory phenomena of the nervous and immune systems. Animals that received morphine and deprived animais that received morphine showed a delay in the development of early reflexes. Neurochemical changes were also observed. BDNF levels in the brainstem were decreased in animals receiving morphine and maternal deprivation. Deprived animals had an increase in NGF levels in the brainstem. Besides, an increase in NGF levels of the cerebral cortex was observed in animals receiving morphine, maternal deprivation and maternal deprivation receiving morphine. A decrease in the nociceptive threshold was observed in animals receiving morphine, maternal deprivation, and maternal deprivation receiving morphine. There were also interactions in the brainstem and cerebral cortex in the levels of BDNF, IL-1β and IL-4 among the independent variables: treatment, deprivation and time, which led to the modification in the central levels of the neuroimmunomodulators evaluated. These data demonstrate the importance of studies focused on the effects of treatment with morphine in the neonatal period throughout life, as well as on the search for therapeutic alternatives that may reverse possible changes due to maternal deprivation in the neonatal period.

Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve certo grau de estresse) durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. Após estes primeiros experimentos procuramos verificar também a capacidade do exercício físico em reverter o prejuízo da memória causado pela separação maternal, procedimento que causa um déficit de memória já descrito pela literatura, utilizando, também, o teste de esquiva inibitória. O estresse diário realçou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo de memória curta (MCD) e de longa duração (MLD) na tarefa do reconhecimento em 2 semanas mas somente de MCD após 8 semanas; e não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício realçou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou MCD e MLD na tarefa do reconhecimento após 2 mas não após 8 semanas; e realçou uma medida importante da aprendizagem espacial após 8 semanas (latência de escape), mas não outras medidas. Em relação ao grupo de animais que foram submetidos à separação maternal verificou-se que o exercício crônico foi capaz de reverter o déficit da MCD e MLD na esquiva inibitória e da MCD no reconhecimento de objetos, mas não teve efeitos sobre o prejuízo da MLD nesta tarefa e sobre a memória espacial testada no Labirinto Aquático de Morris. Portanto, o exercício físico crônico tem uma influência positiva sobre amemória e, adicionalmente, pode ser visto como uma ferramenta terapêutica para reverter determinados déficits de memória. / Here we studied the effects of daily forced exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests were: habituation of exploration in an open field, object recognition and spatial memory in Morris water maze. After these experiments we also tried to verify the physical exercise capacity to revert the memory deficit caused by maternal deprivation, procedure that causes a memory deficit already reported, by means of the inhibitory avoidance test. Daily footshock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task after 2 weeks but only STM after 8 weeks; and had no effect on the spatial task after neither 2 or 8 weeks. The exercise protocol also enhanced habituation in the open field after 2 but not 8 weeks; it hindered STM and LTM in the recognition task after 2 but not at 8 weeks; and it enhanced one important measure of spatial learning after 8 weeks (latency to escape) but not other measures. In relation of the animals that was submitted to maternal deprivation we verified that the exercise is capable to revert the deficit of STM and LTM in inhibitory avoidance test and of STM in object recognition test, but don’t have any effect on the prejudice of LTM in object recognition and in spatial memory verify using the Morris water maze test. Thus, the physical exercise had a positive influence on memory and, additionally, it can be seen like one therapeutic strategy to reverts some memory deficits.

Dor em pediatria tem sido o foco de muitos estudos nas últimas décadas devido ao fato de que neonatos apresentam menor limiar a estímulos nocivos e inócuos em relação aos adultos. Desta forma, o uso de analgésicos é frequente para sedação e analgesia em UTIs pediátricas, e entre os opioides, a morfina é um dos mais utilizados. Adicionalmente, exposição a estímulos estressantes como a deprivação materna está entre os fatores ambientais relacionados a alterações no desenvolvimento neural. O estresse social ou a negligência do cuidado parental, e mais precisamente do cuidado materno em ratos, está associado a importantes alterações comportamentais na vida adulta. Entre estas alterações apresentadas ao longo da vida estão alterações na resposta ao estresse, e à alteração na sensibilidade a estímulos dolorosos, indexadas por hiperalgesia. Consquentemente, o estresse social gerado pela deprivação materna está relacionado a prejuízos cognitivos, emocionais e sociais, além de alterações neuroquímicas de longo prazo. Deste modo, é necessário atenção, prevenção e tratamento a esses eventos físicos, emocionais e comportamentais no período neonatal e durante a infância, uma vez que as bases neurobiológicas envolvidas nestes fenômenos ainda não foram completamente elucidadas. Considerando a relevância do tema, o objetivo deste estudo foi verificar os efeitos do tratamento com 5 μg de morfina, uma vez ao dia, do P8 ao P14 e a exposição a deprivação materna por 3 horas durante os primeiros 10 dias de vida em curto (P16), médio (P30) e longo prazo (P60), sobre o desenvolvimento dos reflexos neuromotores da prole por meio do Reflexo de Endireitamento, Geotaxia Negativa e Marcha; comportamento nociceptivo por meio dos testes Tail-Flick e Placa Quente, respectivamente. Um total de 58 filhotes foi utilizado. Os animais foram divididos em 5 grupos: controle total (C), que não recebeu nenhuma intervenção; salina (S), que recebeu solução salina; morfina (M), que recebeu morfina; deprivado salina (DS), que foram submetidos a deprivação maternal e receberam solução salina; e deprivado morfina (DM), que foram submetidos a deprivação maternal e receberam morfina. Em relação aos testes neuroquímicos, foram analisados níveis de BDNF, NGF, IL-1β e IL-4 em tronco e córtex cerebral que estão relacionados a fenômenos modulatórios em sistemas nervoso e imune. Os animais que receberam morfina e os deprivados maternos que receberam morfina apresentaram atraso no desenvolvimento dos reflexos iniciais. Alterações neuroquímicas também foram observadas. Os níveis de BDNF no tronco encefálico foram diminuídos em animais que receberam morfina e deprivação materna. Animais deprivados apresentaram um aumento nos níveis de NGF no tronco encefálico. Além disso, observou-se um aumento nos níveis de NGF do córtex cerebral em animais que receberam morfina, deprivados maternos e deprivados maternos que receberam morfina. Uma diminuição no limiar nociceptivo foi observada em animais que receberam morfina, deprivados maternos e os deprivados maternos que receberam morfina. Também houve interações em tronco encefálico e córtex cerebral nos níveis de BDNF, IL-1β e IL-4 entre as variáveis independentes: tratamento, deprivação e tempo, o que levou à modificação nos níveis centrais dos neuroimunomoduladores avaliados. Estes dados demonstram a importância de estudos focados nos efeitos do tratamento com morfina no período neonatal ao longo da vida, assim como na busca por alternativas terapêuticas que possam reverter possíveis alterações decorrentes da separação materna no período neonatal. / Pediatric pain has been the focus of many studies in the last decades due to the fact that neonates have a lower threshold for innocuous and noxious stimuli than for adults. Thus, the use of analgesics is frequent for sedation and analgesia in pediatric intensive care units, and among opioids, morphine is one of the most used. Additionally, exposure to stressful stimuli such as maternal deprivation is among the environmental factors related to changes in neural development. The social stress or neglect of parental care, and more precisely maternal care in rats, is associated with important behavioral changes in adult life. Among these changes presented throughout life are changes in the response to stress, and the change in sensitivity to painful stimuli, indexed by hyperalgesia. Consequently, the social stress generated by maternal deprivation is related to cognitive, emotional and social impairments, further to long-term neurochemical changes. Thus, attention, prevention and treatment are necessary to these physical, emotional and behavioral events in the neonatal period and during childhood, since the neurobiological bases involved in these phenomena have not yet been fully elucidated. Considering the relevance of the subject, the objective of this study was to verify the effects of treatment with 5 μg of morphine once a day from P8 to P14 and exposure to maternal deprivation for 3 hours during the first 10 days of short (P16), medium (P30) and long- term (P60), on the development of neuromotor reflexes of offspring through the righting Reflex, Negative Geotaxis and Gait; nociceptive behavior through the Tail-Flick and Hot Plate tests, respectively. A total of 58 puppies were utilized. The animals were divided in 5 groups: the total control group (C), which did not receive any intervention; saline group (S), which receive saline solution; morphine group (M), which receive morphine; deprived saline (DS), which were subjected to maternal deprivation and receive saline solution; and deprived morphine group (DM), which were subjected to maternal deprivation and receive morphine. In relation to the neurochemical tests, levels of BDNF, NGF, IL-1β and IL-4 were analyzed in the brainsteam and cerebral cortex and are related to modulatory phenomena of the nervous and immune systems. Animals that received morphine and deprived animais that received morphine showed a delay in the development of early reflexes. Neurochemical changes were also observed. BDNF levels in the brainstem were decreased in animals receiving morphine and maternal deprivation. Deprived animals had an increase in NGF levels in the brainstem. Besides, an increase in NGF levels of the cerebral cortex was observed in animals receiving morphine, maternal deprivation and maternal deprivation receiving morphine. A decrease in the nociceptive threshold was observed in animals receiving morphine, maternal deprivation, and maternal deprivation receiving morphine. There were also interactions in the brainstem and cerebral cortex in the levels of BDNF, IL-1β and IL-4 among the independent variables: treatment, deprivation and time, which led to the modification in the central levels of the neuroimmunomodulators evaluated. These data demonstrate the importance of studies focused on the effects of treatment with morphine in the neonatal period throughout life, as well as on the search for therapeutic alternatives that may reverse possible changes due to maternal deprivation in the neonatal period.

Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve certo grau de estresse) durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. Após estes primeiros experimentos procuramos verificar também a capacidade do exercício físico em reverter o prejuízo da memória causado pela separação maternal, procedimento que causa um déficit de memória já descrito pela literatura, utilizando, também, o teste de esquiva inibitória. O estresse diário realçou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo de memória curta (MCD) e de longa duração (MLD) na tarefa do reconhecimento em 2 semanas mas somente de MCD após 8 semanas; e não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício realçou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou MCD e MLD na tarefa do reconhecimento após 2 mas não após 8 semanas; e realçou uma medida importante da aprendizagem espacial após 8 semanas (latência de escape), mas não outras medidas. Em relação ao grupo de animais que foram submetidos à separação maternal verificou-se que o exercício crônico foi capaz de reverter o déficit da MCD e MLD na esquiva inibitória e da MCD no reconhecimento de objetos, mas não teve efeitos sobre o prejuízo da MLD nesta tarefa e sobre a memória espacial testada no Labirinto Aquático de Morris. Portanto, o exercício físico crônico tem uma influência positiva sobre amemória e, adicionalmente, pode ser visto como uma ferramenta terapêutica para reverter determinados déficits de memória. / Here we studied the effects of daily forced exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests were: habituation of exploration in an open field, object recognition and spatial memory in Morris water maze. After these experiments we also tried to verify the physical exercise capacity to revert the memory deficit caused by maternal deprivation, procedure that causes a memory deficit already reported, by means of the inhibitory avoidance test. Daily footshock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task after 2 weeks but only STM after 8 weeks; and had no effect on the spatial task after neither 2 or 8 weeks. The exercise protocol also enhanced habituation in the open field after 2 but not 8 weeks; it hindered STM and LTM in the recognition task after 2 but not at 8 weeks; and it enhanced one important measure of spatial learning after 8 weeks (latency to escape) but not other measures. In relation of the animals that was submitted to maternal deprivation we verified that the exercise is capable to revert the deficit of STM and LTM in inhibitory avoidance test and of STM in object recognition test, but don’t have any effect on the prejudice of LTM in object recognition and in spatial memory verify using the Morris water maze test. Thus, the physical exercise had a positive influence on memory and, additionally, it can be seen like one therapeutic strategy to reverts some memory deficits.

Many women in prison are likely to have children, but for various reasons may not be playing the role of primary caregiver prior to incarceration, and may be unable to fulfill this role when released. This research was designed to investigate the interpersonal difficulties that may contribute to the parenting problems of this unique population. Female offenders have an increased likelihood of personality pathology and history of abuse, creating a set of circumstances that affect these women's ability to have satisfactory relationships. This may be manifested in an orientation towards relationships that could be classified as an insecure attachment style, although it is not the relationship per se that is classified as an insecure attachment style; rather, the insecure attachment style (or pattern) refers to the individual's view of themselves and others, and their attachment style may then influence their responses to others in intimate relationships (e.g., their warmth, caregiving, jealousy, ability to trust, etc). The female offender population provides a distinctive opportunity for investigating the relationships between attachment styles and incarcerated women's personality pathology, experiences with their primary caregivers, as well as their own experiences as mothers. The attachment styles of one hundred eleven incarcerated female inmates were assessed using the Relationship Questionnaire (RQ; Bartholomew & Horowitz, 1991) and the Experience in Close Relationships Inventory (ECRI; Brennan, Clark, & Shaver, 1998), and a sub-sample of these women were interviewed using the Peer Attachment Interview (Bartholomew & Horowitz, 1991). Offenders were also assessed for quality of relationships with parents using the Egna Minnen Betraffande Uppfostran (EMBU; Perris, Jacobsson, Lindstrom, von Knorring, & Perris, 1980), as well as with children using the Parental Stress Scale (PSS; Berry & Jones, 1995) and a Parental Bonding Interview (created specifically for this research to gather information about parent-child relationships, the level of caregiving provided to the child, and the mother's subjective account of her parenting experiences). The SCID-Il Clinical Interview (First, Gibbon, Spitzer, Williams, & Benjamin, 1997) was used to assess for personality disorder characteristics, which have been found in previous research to be prevalent in female offender populations. It was found that three-quarters of the women in the sample had given birth to children, however, 88.4% were no longer playing the role of primary caregiver upon incarceration. Nearly 61% of respondents claimed that social services had taken at least one child away, and 38.2% claimed that they had voluntarily given their children away. Reasons for no longer having custody varied, but the majority of women (70%) reported that drug and alcohol abuse was a major factor. Further, it was found that women in the sample were characterized by insecure attachment styles. Characteristics of personality disorders were present in over 73% of the sample. Results showed a high rate of abuse in childhood by primary caregivers, high levels of parental rejection, and low levels of parental warmth. In addition, participants reported unstable relationships with the fathers of their children. Further, the presence of an insecure attachment style was related to higher mean number of personality disorder characteristics, higher reported means of maternal and paternal rejection, and higher reported means of emotional and physical abuse by fathers. Impression management was found to be an issue with the respect to the majority of the measured utilized in the research. The goal of this research was to attain a greater understanding of the interpersonal difficulties of the female offender population, and how family, romantic, and peer relationships are related to parenting difficulties for these women. These issues, as well as limitations surrounding the use of current attachment measures, are discussed herein. / Arts, Faculty of / Psychology, Department of / Graduate

Indiana University-Purdue University Indianapolis (IUPUI) / Early life trauma is a risk factor for a number of neuropsychiatric disorders, including schizophrenia (SZ) and depression. Animal models have played a critical role in understanding how early-life trauma may evoke changes in behavior and biomarkers of altered brain function that resemble these neuropsychiatric disorders. However, since SZ is a complex condition with multifactorial etiology, it is difficult to model the breadth of this condition in a single animal model. Considering this, it is necessary to develop rodent models with clearly defined subsets of pathologies observed in the human condition and their developmental trajectory. Episodic memory is among the cognitive deficits observed in SZ. Theta (6-10 Hz), low gamma (30-50 Hz), and high gamma (50-100 Hz) frequencies in the hippocampus (HC) are critical for encoding and retrieval of memory. Also, theta-gamma comodulation, defined as correlated fluctuations in power between these frequencies, may provide a mechanism for coding episodic sequences by coordinating neuronal activity at timescales required for memory encoding and retrieval. Given that patients with SZ have impaired recognition memory, the overall objectives of these experiments were to assess local field potential (LFP) recordings in the theta and gamma range from the dorsal HC during a recognition memory task in an animal model that exhibits a subclass of symptoms that resemble SZ. In Aim 1, LFPs were recorded from the HC to assess theta and gamma power to determine whether rats that were maternally deprived (MD) for 24-hrs on postnatal day (PND 9), had altered theta and high/low gamma power compared to sham rats during novel object recognition (NOR). Brain activity was recorded while animals underwent NOR on PND 70, 74, and 78. In Aim 2, the effects of theta-low gamma comodulation and theta-high gamma comodulation in the HC were assessed during NOR between sham and MD animals. Furthermore, measures of maternal care were taken to assess if high or low licking/grooming behaviors influenced recognition memory. It was hypothesized that MD animals would have impaired recognition memory and lower theta and low/high gamma power during interaction with both objects compared to sham animals. Furthermore, it was hypothesized that sham animals would have higher theta-gamma comodulation during novel object exploration compared to the familiar object, which would be higher than the MD group. Measures of weight, locomotor activity, and thigmotaxis were also assessed. MD animals were impaired on the NOR task and had no change in theta or low/high gamma power or theta-gamma comodulation when interacting with the novel or familiar object during trials where they performed unsuccessfully or successfully. However, higher theta and gamma power and theta-gamma comodulation was observed in sham animals depending on the object they were exploring or whether it was a successful or unsuccessful trial. These data indicate altered functioning of the HC following MD and a dissociation between brain activity and behavior in this group, providing support that early life trauma can induce cognitive and physiological impairments that are long-lasting. In conclusion, these data identify a model of early life stress with a translational potential, given that there are points of contact between human studies and the MD model. Furthermore, these data provide a set of tools that could be used to further explore how these altered neural mechanisms may influence cognition and behavior.

É crescente o interesse nos efeitos que o ambiente parental exerce sobre o fenótipo da prole, a chamada herança epigenética. Tem sido mostrado que essa herança ocorre especialmente para efeitos de plasticidade do desenvolvimento, os quais derivam de alteração ambiental durante o desenvolvimento parental. Dentre os estudados realizados em camundongos, várias estratégias ambientais foram abordadas, como o estresse durante a infância e o enriquecimento ambiental, com a avaliação da prole em relação a parâmetros comportamentais, fisiológicos e moleculares. De modo a estudar o fenômeno, o presente trabalho investigou, em camundongos Swiss machos, os efeitos de um estresse durante a infância, a Privação Materna em PND 9, com avaliação de comportamentos exploratório (Campo Aberto), do tipo ansioso (Labirinto em Cruz Elevado), depressivo (Nado Forçado) e relacionados ao álcool (Condicionamento Condicionado por Lugar e Sensibilização Comportamental), e, numa outra abordagem, do Enriquecimento Ambiental do desmame (PND 21) à idade adulta (PND 70), com avaliação de parâmetros fisiológicos diversos (peso corporal, de depósito de gordura, de baço e glândulas adrenais) e comportamentos exploratório (Campo Aberto), memória espacial (Labirinto de Barnes), dominância social (Tubo de Dominância Social), atratividade (Teste de Escolha de Parceiro), além de avaliação de corticosterona plasmática e BDNF hipocampal. A privação materna não promoveu diferenças para os parâmetros comportamentais avaliados. Optou-se pela utilização do paradigma do Enriquecimento Ambiental para investigação dos efeitos sobre o fenótipo da prole (machos e fêmeas). Foram observados nos filhotes machos resultados comportamentais opostos aos apresentados pela geração paterna. Porém, quando os filhos foram expostos a um período breve de enriquecimento durante a idade adulta, essas diferenças não foram mais encontradas. Portanto, conclui-se que o enriquecimento ambiental paterno foi capaz de gerar efeitos na prole, tornando os filhotes machos menos adaptados ao ambiente não enriquecido. / There is a growing interest in the effects of the parental environment on the offspring phenotype, the so-called epigenetic inheritance. It has been shown that this inheritance occurs especially for developmental plasticity effects, which stem from environmental changes during parental development. Studies carried out in mice have adopted several environmental strategies, such as early life stress and environmental enrichment, and the offspring have been assessed for behavioural, physiological and molecular parameters. In order to study the phenomenon, the present work investigated, in Swiss male mice, the effects of an early-life stress protocol, the Maternal Deprivation on PND 9, assessing behaviours such as exploratory (Open Field), anxiety-like (Elevated-Plus Maze), depressive-like (Forced Swim) and alcohol-related behaviours (Conditioned Place Preference and Behavioural Sensitisation) and, through a different approach, the environmental enrichment, from weaning (PND 21) to adulthood (PND 70), assessing diverse physiological parameters (body weight, fat pad weight, spleen and adrenal glands weights) and behaviours such as exploratory (Open Field), spatial memory (Barnes Maze), social dominance (Social Dominance Tube Test), attractiveness (Mate Choice Teste) as well as plasmatic corticosterone and hippocampal BDNF. The maternal deprivation did not yield any differences in the behavioural parameters assessed. The Environmental Enrichment paradigm was adopted for studying its effects on the offspring phenotype (males and females). Behavioural results were observed in the male offspring, which were the opposite of those found in the paternal generation. However, when the male offspring was exposed to a brief period of enrichment during adulthood, these differences were no longer found. Therefore, paternal environmental enrichment was able to induce effects on the offspring, turning male offspring less adapted to the non-enriched environment.