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Grayson, Ben. "Validation of an animal model of cognitive dysfunction associated with schizophrenia : development and validation of the novel object recognition task using behavioural manipulations and psychotomimetic dosing regimens to induce cognitive deficits of relevance to schizophrenia in hooded-Lister rats." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5481.
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Phencyclidine (PCP) is a non-competitive NMDA receptor antagonist that has been shown to induce schizophrenia-like psychotic symptoms that are clinically indistinguishable from schizophrenia in patients. When administered to rodents, PCP produces an array of behaviours that are characteristic of schizophrenia. Schizophrenia is associated with continual and treatment resistant cognitive deficits which are now recognised as a core feature of the disease. The aim of the studies reported in chapter 3 were to establish a set of objects with equal preference in the NOR (novel object recognition) test. Furthermore, the inter-trial-interval (ITI) of the NOR test was investigated in an attempt to elucidate the effects of time and location of the rats during the ITI on the cognitive impairments following sub-chronic PCP treatment. The experiments in chapter 4 were designed to compare the performance of male and female rats in the NOR test following treatment with acute d-amphetamine (d-amph), PCP and sub-chronic PCP treatment. In chapter 5, validation of the cognitive deficits induced by sub-chronic PCP treatment was assessed using carefully selected pharmacological agents. The aim of the studies in chapter 6 was to determine the effects of isolation rearing on cognitive performance in the NOR test following increasing ITIs. Additionally, the sensitivity of isolation reared rats compared to social controls following acute administration of PCP and d-amph was assessed using the NOR test. Studies in chapter 8 utilised the 16-holeboard maze to determine the effects of acute treatment with d-amphetamine, PCP and scopolamine on working memory in the rat. NOR is a visual learning and memory test that measures recognition memory which is impaired in patients with schizophrenia. Studies presented in this thesis demonstrate the importance of careful pilot studies when selecting objects for use in the NOR test. Initial studies in sub-chronic PCP (2 mg/kg for 7 days followed by 7 days drug free) treated female hooded-Lister rats revealed a preference of the rats for the wooden cone object; subsequently this object was eliminated from further NOR experiments. Sub-chronic PCP treated rats were found to be highly susceptible to the disruptive influence of distraction during the short 1 min inter-trial-interval (ITI) in the NOR test. These results are consistent with clinical findings of the effects of distraction on cognition in schizophrenia patients. Following the initial validation experiments, a 1 min ITI in the home cage was selected for all subsequent NOR studies. Further experiments provided evidence to confirm that information presented in the acquisition trial is encoded but not retained in the retention trial of the NOR test by IV PCP-treated rats. Male rats were less sensitive to the recognition memory deficits induced by acute treatment with PCP and d-amphetamine compared with females. Following sub-chronic PCP treatment, both males and females showed object recognition deficits, however, the impairments were more robust in female rats. Female rats were therefore selected for all subsequent experiments. Pharmacological validation was carried out using carefully selected agents which were assessed for their ability to restore the sub-chronic PCP induced cognitive deficit in the object recognition test. It was found that the classical antipsychotic agents haloperidol and fluphenazine, the benzodiazepine anxiolytic chlordiazepoxide and the SSRI antidepressant fluoxetine were ineffective. Further studies showed that the atypical antipsychotic agents, clozapine and risperidone, the analeptic agent modafinil, the nAChR full agonist nicotine, and full agonist and positive allosteric modulator of the α7 nAChR (PNU-282987 and PNU120596 respectively) reversed the recognition memory deficit induced by sub-chronic PCP treatment in the NOR test. Isolation rearing of rats at weaning is an environmental stressor that has relevance for modelling the symptomatology and pathology of schizophrenia. Isolates had a significantly increased locomotor activity (LMA) response to a novel environment and enhanced sensitivity to time delay-induced recognition memory deficits, compared with their socially reared counterparts. Isolates were less sensitive to an acute PCP-induced recognition memory deficit but more sensitive to an acute d-amphetamine induced recognition memory deficit in the NOR test compared to social controls. Preliminary results from the 16-holeboard maze experiments reveal that acute administration of the mAChR antagonist scopolamine, d-amphetamine, PCP and sub-chronic PCP treatment reduced working memory scores compared to vehicle treated controls. Taken together, these findings suggest that sub-chronic treatment with PCP induces cognitive deficits in behavioural tests of relevance to cognition associated with schizophrenia. This may allow the detection of novel pharmacotherapies to alleviate these cognitive deficits and exploration of the nature of cognitive disturbances in these patients.
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Giannarou, Stamatia. "Novel techniques for object recognition." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486609.
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This thesis is concerned with the design of a real time object recognition system. The ultimate goal is to create a cognitive vision system which is robust across environmental changes (causing partial occlusions and cluttered backgrounds). invariant to image transformations (translation, rotation and scaling) and insensitive to intra-category appearance variations (permit recognition of perceptually similar objects that are not mathematically identical). . Initially. a new framework which allows for the guantitative combination of a pre-selected set of edge detectors based on the correspondence between their outcomes is proposed as an essential preprocessing stage of an object detector that operates on edge maps. This is inspired from the problem that despite the enormous amount of literature on edge detection techniques, there is no single one that performs well in every possible image context. Two approaches are proposed for this purpose; the so called Receiver Operating Characteristics (ROC) analysis and Kappa Statistics. For efficient object detection, a novel technigue for the automatic identification of real world objects in complex scenes using Shape Context analysis and multi-stage clustering is introduced. The identification problem requires the comparison of assemblies of image regions with a previously stored view of a known prototype. Shape context representation and matching are employed for recovering point correspondences between the image and the prototype. A multistage type of clustering of suspicious image locations is applied in a novel fashion to enable the identification of regions of interest on the complex scene. based on a set of density and figural continuity metrics. Finally. a novel shape signature matching approach for the automatic identification of real world objects in complex scenes is also proposed. The identification process is applied on isolated objects and requires the segmentation of the image into separate objects. followed by the extraction of representative shape features and the similarity estimation of pairs of objects. In order to enable an efficient object representation, a novel boundary-based shape descriptor is introduced, formed by a set of one dimensional signals called shape signatures. Two different approaches are proposed for the shape signature comparison. In the first approach, the cross-correlation metric is used in a novel fashion to gauge the degree of similarity between objects. In the second approach, the correspondence between the signatures' extreme points is established and is used as a basis for the similarity evaluation
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Oliveira, Gabriel Leivas. "Sparse Spatial Coding: a novel approach for efficient and accurate object recognition." Universidade Federal de Minas Gerais, 2012. http://hdl.handle.net/1843/ESBF-8SVMLB.
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Successful state-of-the-art object recognition techniques from images have been based on powerful techniques, such as sparse representation, in order to replace the also popular vector quantization approach. Recently, sparse coding, which is characterized by representing a signal in a sparse space, has raised the bar on sev-eral object recognition benchmarks. However, one serious drawback of sparse space based methods is that similar local features can be quantized into different visual words. We present in this thesis a new object recognition approach, called Sparse Spa-tial Coding (SSC), which combines a sparse coding dictionary learning and a spatial constraint coding stage. Thus, we minimize the problems of pure sparse represen-tations. Experimental evaluation was done at Caltech 101, Caltech 256, Corel 5000 and Corel 10000, that are datasets specifically designed to object recognition evalu-ation. The obtained results show that, to the best of our knowledge, our approach achieves accuracy beyond the best single feature method previously published on the databases. The method also outperformed, for the same bases, several methods that use multiple feature, and provide equivalent to or slightly lower results than other techniques. Finally, we verify our method generalization, applying the SSC to recognize scene in the Indoor 67 scene dataset, VPC and COLD, displaying perfor-mance comparable to state-of-the-art approaches in the first two bases and superior in COLD dataset.Até recentemente o reconhecimento de objetos, um problema clássicodaVisãoCom-putacional, vinha sendo abordado por técnicas baseadas em quantização vetorial. Entretanto, atualmente, abordagens que utilizam representação esparsa tem ap-resentado resultados significativamente superiores às técnicas usuais. Entretanto, uma desvantagem de métodos baseados em representação esparsa é o fato de car-acterísticas similares poderem ser quantizadas por conjuntos diferentes de palavras visuais. Esta dissertação apresenta um novo método de reconhecimento de objetos de-nominado SSC Sparse Spatial Coding o qual é caracterizado pelo aprendizado do dicionário utilizando representação esparsa e codificação baseada em restrição es-pacial. Dessa forma, minimiza-se significativamente o problema típico encontrado em representações estritamente esparsas. A avaliação do SSC foi realizada por meio de experimentos aplicando-o às bases Caltech 101, Caltech 256, Corel 5000 e Corel 10000, criadas especificamente para avaliação de técnicas de reconhecimento de objetos. Os resultados obtidos demonstram desempenho superior aos reportados na literatura até o momento para os métodos que utilizam um único descritor. O método também superou, para as mesmas bases, vários outros métodos que utilizam múltiplas características, e apre-sentou desempenho equivalente ou apenas ligeiramente inferior a outras técnicas. Finalmente, para verificarmos a generalização, o SSC foi utilizado para o reconheci-mento de cenas nas bases Indoor 67, VPC e COLD tendo apresentado desempenho comparável ao de abordagens do estado da arte para as duas primeiras bases e su-perior na base COLD.
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Fotiadis, Dimitrios. "Novel shape representation strucutres for object recognition, retrieval, and plant taxonomic identification purposes." Thesis, University of Surrey, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502625.
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Malik, Qurrat-ul-Ain. "Novel methods of object recognition and fault detection applied to non-destructive testing of rail's surface during production." Thesis, Manchester Metropolitan University, 2013. http://e-space.mmu.ac.uk/314012/.
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A series of rail image inspection algorithms have been developed for Tata Steels Scunthorpe rail production line. The following thesis describes the contributions made by the author in the design and application of these algorithms. A fully automated rail inspection system that has never been implemented before in any such company or setup has been developed. An industrial computer vision system (JLI) already exists for the image acquisition of rails during production at a rail manufacturing plant in Scunthorpe. An automated inspection system using the same JLI vision system has been developed for the detection of rail‟s surface defects during manufacturing process. This is to complement the human factor by developing a fully automated image processing based system to recognize the faults with an improved efficiency and to allow an exhaustive detection on the entire rail in production. A set of bespoke algorithms has been developed from a plethora of available image processing techniques to extract and identify components in an image of rail in order to detect abnormalities. This has been achieved through offline processing of the rail images using the blended use of different object recognition and image processing techniques, in particular, variation of standard image processing techniques. Several edge detection methods as well as adapted well known Artificial Neural Network and Principal Component Analysis techniques for fault detection on rail have been developed. A combination of customised existing image algorithms and newly developed algorithms have been put together to perform the efficient defect detection. The developed system is fast, reliable and efficient for detection of unique artefacts occurring on the rail surface during production followed by fault classification on the rail imaging system. Extensive testing shows that the defect detection techniques developed for automated rail inspection is capable of detecting more than 90% of the defects present in the available data set of rail images, which has more than 100,000 images under investigation. This demonstrates the efficiency and accuracy of the algorithms developed in this work.
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Adlington, R. L. "The influence of surface detail on object identification in Alzheimer's patients and healthy participants." Thesis, University of Hertfordshire, 2009. http://hdl.handle.net/2299/4004.
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Image format (Laws, Adlington, Gale, Moreno-Martínez, & Sartori, 2007), ceiling effects in controls (Fung et al., 2001; Laws et al., 2005; Moreno-Martínez, & Laws, 2007; 2008), and nuisance variables (Funnell & De Mornay Davis, 1996; Funnell & Sheridan, 1992; Stewart, Parkin & Hunkin, 1992) all influence the emergence of category specific deficits in Alzheimer‟s dementia (AD). Thus, the predominant use of line drawings of familiar, everyday items in category specific research is problematic. Moreover, this does not allow researchers to explore the extent to which format may influence object recognition. As such, the initial concern of this thesis was the development of a new corpus of 147 colour images of graded naming difficulty, the Hatfield Image Test (HIT; Adlington, Laws, & Gale, 2009), and the collection of relevant normative data including ratings of: age of acquisition, colour diagnosticity, familiarity, name agreement, visual complexity, and word frequency. Furthermore, greyscale and line-drawn versions of the HIT corpus were developed (and again, the associated normative data obtained), to permit research into the influence of image format on the emergence of category specific effects in patients with AD, and in healthy controls. Using the HIT, several studies were conducted including: (i) a normative investigation of the effects of category and image format on naming accuracy and latencies in healthy controls; (ii) an exploration of the effects of image format (using the HIT images presented in colour, greyscale, and line-drawn formats) and category on the naming performance of AD patients, and age-matched controls performing below ceiling; (iii) a longitudinal investigation comparing AD patient performance to that of age-matched controls, on a range of semantic tasks (naming, sorting, word-picture matching), using colour, greyscale, and line-drawn versions of the HIT; (iv) a comparison of naming in AD patients and age-matched controls on the HIT and the (colour, greyscale and line-drawn) images from the Snodgrass and Vanderwart (1980) corpus; and (v) a meta-analysis to explore category specific naming in AD using the Snodgrass and Vanderwart (1980) versus other corpora. Taken together, the results of these investigations showed first, that image format interacts with category. For both AD patients and controls, colour is more important for the recognition of living things, with a significant nonliving advantage emerging for the line-drawn images, but not the colour images. Controls benefitted more from additional surface information than AD patients, which chapter 6 shows results from low-level visual cortical impairment in AD. For controls, format was also more important for the recognition of low familiarity, low frequency items. In addition, the findings show that adequate control data affects the emergence of category specific deficits in AD. Specifically, based on within-group comparison chapters 6, 7, and 8 revealed a significant living deficit in AD patients. However, when compared to controls performing below ceiling, as demonstrated in chapters 7 and 8, this deficit was only significant for the line drawings, showing that the performance observed in AD patients is simply an exaggeration of the norm.
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Bullard, Laura Ashley. "An Animal Model of Flashbulb Memory: Insights into the Time-Dependent Mechanisms of Memory Enhancement." Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5917.
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The vivid memory of an emotional event, as well as memory for incidental details associated with the arousing event, has been referred to collectively as a “flashbulb memory”. An important aspect of flashbulb memory in people is that an emotional event enhances memory of contextual details, such as the weather, or clothes one was wearing at the time of the event. Therefore, an emotional event not only produces a detailed memory of the event, itself, but also enhances memory for contextual details that would otherwise not be remembered. The first goal of this work is to describe the development of my animal model of flashbulb memory, including a discussion of the importance of the timing between an emotional event and incidental, contextual cues. The second goal is to address the time-dependent neuroendocrine processes involved in stress-induced memory enhancement in rats. The involvement of brain structures, namely the hippocampus and amygdala, and hormones, including corticosterone and epinephrine, that interact to produce a composite memory of the contextual cues occurring in close temporal proximity to an emotional event are discussed. The results of Experiment 1 validate the animal model of flashbulb memory whereby an emotional event (predator exposure) produced memory for context cues that, under control conditions, would be forgotten. This memory enhancement only occurred when the emotional event was close in temporal proximity to training in the task. Experiment 2 provided evidence that epinephrine administration close in time to training mimicked the context memory formation induced by brief predator exposure, while propranolol, a β-adrenergic antagonist, as well as CPP, an NMDA receptor antagonist, blocked this effect. The results of Experiment 3 revealed that propranolol, CPP, and dexamethasone also blocked the brief predator stress-induced context memory formation. The results of Experiment 4 revealed that cannulated animals infused with aCSF (control) did not show evidence of predator stress-induced memory, therefore methodological issues within this experiment are addressed. Finally, the results of Experiment 5 revealed that adrenalectomy eliminated the predator stress-induced context memory compared to sham operated animals, suggesting that endogenous stress hormones are required for stress-induced context memory formation. Further, adrenalectomized rats supplemented with epinephrine before training did show evidence of context memory enhancement suggesting that epinephrine eliminated the memory impairment produced by adrenalectomy, and was sufficient to enhance memory in the absence of corticosterone. Overall this approach has provided insight into the time-dependent neuroendocrine processes involved in the formation of flashbulb, and potentially traumatic, memories in people.
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Halonen, Joshua D. "Influence of temporary inactivation of the prefrontal cortex of hippocampus during stress on the subsequent expression of anxiety and memory." [Tampa, Fla] : University of South Florida, 2009. http://purl.fcla.edu/usf/dc/et/SFE0002880.
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Maurmann, Natasha. "Avaliação pré-clínica de atividades biológicas de moléculas de Mangifera indica e de Valeriana glechomifolia." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2010. http://hdl.handle.net/10183/28432.
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Neste estudo avaliamos atividades biológicas pré-clínicas de moléculas obtidas de Mangifera indica e de Valeriana glechomifolia. Mangiferina, isolada de M. indica, estimulou a proliferação celular e induziu um aumento significativo na secreção do fator de crescimento do nervo e do fator de necrose tumoral em células de glioblastoma humano U138-MG in vitro. Uma injeção sistêmica de mangiferina melhorou a consolidação da memória de longa duração (LTM) de reconhecimento de objetos (RO) e prejudicou a retenção da memória aversiva no teste da esquiva inibitória (EI) em ratos. A melhora da LTM no RO promovida pela administração sistêmica de mangiferina também foi observada com a administração intrahipocampal. Já o prejuízo da memória no teste da EI observado sistemicamente não ocorreu com a infusão no hipocampo ou amígdala. Camundongos atáxicos também apresentaram melhora na memória de RO após administração crônica de mangiferina, sem efeito na EI; um extrato comercializado de M. indica não afetou a memória no RO, mas facilitou a memória na EI. Os resultados indicam que mangiferina melhora a LTM no RO com envolvimento do hipocampo por meio de um mecanismo que pode envolver um aumento dos níveis da neurotrofina NGF e da citocina TNF-α. Valepotriatos, isolados de V. glechomifolia, demonstraram inibição da viabilidade de células tumorais U138-MG nas doses de 30 e 100μg/μl; o 8-Br- AMPc, um análogo do AMPc, atenuou à inibição dos valepotriatos na viabilidade celular, sugerindo que os valepotriatos interagem com a rota de sinalização celular do AMPc/PKA na inibição da viabilidade de células cancerosas. A administração sistêmica de valepotriatos, em camundongos 30 minutos antes dos testes, apresentou os seguintes resultados: durante a exploração no campo aberto, a dose 10mg/kg causou redução na locomoção e no comportamento exploratório e diminuição da ansiedade no teste do labirinto em cruz elevado. Não ocorreu diferença entre os tratamentos na memória de EI e na memória RO, exceto no grupo que recebeu 3mg/kg de valepotriatos que apresentou piora na LTM de RO. Os resultados indicam que os valepotriatos causaram atividades ansiolítica e sedativa sem déficits na memória de EI e RO em camundongos tratados com 10mg/kg. As atividades biológicas in vitro e in vivo encontradas nas moléculas estudadas (especialmente mangiferina e valepotriatos) geram interesse de investigações para utilizações terapêuticas na memória e no câncer.We evaluated the biological activities of molecules obtained from Mangifera indica and Valeriana glechomifolia. Mangiferin, isolated from M. indica, stimulated cell proliferation and induced a significant increase in levels of nerve growth factor and tumor necrosis factor secreted in human glioblastoma cells U138-MG in vitro. A systemic injection of mangiferin improved long term memory (LTM) consolidation of object recognition (NOR) and impaired memory retention in aversive inhibitory avoidance test (IA) in rats. The improvement in NOR memory promoted by systemic administration of mangiferin was also observed with intrahippocampal administration. The memory impairment observed systemically in the IA did not occur with the infusion into the hippocampus or amygdala. Ataxic mice also showed improvement in NOR memory after chronic administration of mangiferin, with no effect on IA; a standardized extract of M. indica had not effect on memory in NOR, but facilitated the memory in IA. The results indicate that mangiferin improvement NOR memory involving the hippocampus through a mechanism that may involve increased levels of neurotrophins and cytokines. Valepotriates isolated from V. glechomifolia showed inhibition of the viability of U138-MG tumor cells at doses of 30 and 100μg/μl; 8-BrcAMP, an analogue of cAMP, reversed the inhibition of valepotriates on cell viability, suggesting that valepotriates interact with the cAMP/PKA signaling route in the inhibition of the viability of cancer cells. Systemic administration of valepotriates in mice, 30 minutes before tests, showed the following results: during the open-field, the dose of 10mg/kg caused a reduction in locomotion and exploratory behavior and decreased anxiety in the test of elevated plus maze. There was no difference between treatments in IA or NOR memories, except from the group receiving valepotriates at 3mg/kg, which worsened in the NOR. The results indicated that valepotriates at 10mg/kg caused anxiolytic and sedative activities without inducing memory deficits in IA and NOR. The biological activities in vitro and in vivo found with the studied molecules (notable mangiferin and valepotriates) support further research for potential therapeutic uses in cancer and in memory.
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Sundman, Ann-Sofie. "Personality in piglets : Is there a difference in personality traits between pigs from different teat order positions?" Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69596.
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The objective of this study was to determine whether piglets from different positions in the teat order differ inpersonality. Teat order is established within the first days after birth and from that time, piglets basically suckle fromthe same teat pair until weaning. Three piglets from each of 21 litters (n = 63) were chosen for their place in teatorder; one from anterior teats (A), one from middle teats (B), and one from rear teats (C). The piglets were observedduring suckling, undisturbed behaviour, a novel object test and a straw test. A total of 13 behaviours were registered.A significant difference (P < 0.05) between A, B and C piglets was found in the frequency of disputes duringsuckling, where B piglets were most involved in disputes and C piglets least involved, and a tendency (P < 0.1) wasfound in frequency of undisturbed playing and exploration. A piglets played and explored most, and C piglets least.Four interesting components were found with principal component analysis, explaining 62.4 % of the total variation.These represent personality traits tentatively named exploration, playfulness, food interest and straw interest. Therewere no significant differences in personality type between A, B and C piglets although a tendency that A pigletswere most playful and C piglets were least playful was found. Hence, this study suggests that there might be acorrelation between teat order position and personality.
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Werner, Jade Elizabeth. "Use of Hair Cortisol Analysis to Evaluate the Influence of Housing Systems on Long-Term Stress in Horses." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1592082506300566.
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Cyrenne, De-Laine. "Developmental and sex differences in responses to novel objects : an exploration of animal models of sensation seeking behaviour." Thesis, University of St Andrews, 2012. http://hdl.handle.net/10023/2550.
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Human adolescents exhibit higher levels of sensation seeking behaviour than younger or older individuals, and sensation seeking is higher in males than females from adolescence onwards. Data suggest that changes in gonadal hormone levels during adolescence and differences in the dopamine neurotransmitter system are the bases for why some people exhibit sensation seeking behaviour while others do not. However, causal relationships between physiology and behaviour have been difficult to establish in humans. In order to explore the physiological influences on novelty-seeking behaviour, we looked at response to novelty in a laboratory rodent. This research examined responses to novelty in the conditioned place preference (CPP) task and the novel object recognition (NOR) task in Lister-hooded rats, and assessed the benefits and limitations of each methodology. While the CPP task was not found to provide a reliable measure of response to novelty, the NOR task was more successful. In order to understand the ontogeny of sex differences in novelty responses, both males and females were tested from adolescence through to adulthood. While no sex difference was found in adults in the NOR test, mid-adolescent males exhibited higher novelty preference behaviour than either younger or older males, or females at each stage of development. Since gonadal hormones levels rise during adolescence, a pharmacological agent (a gonadotrophin-releasing hormone antagonist) was used to suppress gonadal hormone levels from early adolescence before again examining responses on the NOR test at mid-adolescence. Gonadal hormone suppression from early adolescence onwards eliminated the sex difference in the NOR test at mid-adolescence by reducing the male response to novelty, while no difference was measured in the female animals. These findings suggest that gonadal hormones play a significant role in the development of response to novelty, especially in males, and the implications for our understanding of human sensation-seeking behaviour are discussed.
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Gomes, Guilherme Monteiro. "Modulação do sistema das poliaminas e bloqueio seletivo de correntes de K+ do tipo A reverte o dano cognitivo induzido por peptídeo β-amiloide25-35." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/4483.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoIn Alzheimer s disease (AD), β-amyloid peptide (Aβ) has been linked with synaptic loss and cognitive dysfunction, albeit the precise mechanism remains unknown. An involvement of N-Methyl-D-Aspartate receptors (NMDAR) in AD is proposed, since its inhibition attenuates some aspects of AD s neuropathology. In this regard, polyamines, like spermidine and spermine, positive modulators of NMDARs, have been shown to have both concentration and synthesis increased by Aβ. Using the novel object recognition task we showed that negative modulation of polyamine system, been trough blockade of its binding site at NMDAR by arcaine (0.02 nmol/site), traxoprodil (0.002 nmol/site), or inhibition of polyamine synthesis by DFMO (2.7 nmol/site), reverses Aβ25-35-induced memory impairment in mice. The activation of polyamine binding site at NMDAR located at extrasynaptic sites might underlie the cognitive deficits of Aβ25-35-treated mice, since incubation of hippocampal neuron cultures with spermidine (400 μM) or Aβ25-35 (10 μM) significantly increased nuclear accumulation of jacob protein, a marker of extrasynaptic NMDAR activation. Moreover, traxoprodil (4nM), arcaine (4 μM) or DFMO (5 μM) blocked the Aβ-induced jacob nuclear translocation. Activation of extrasynaptic NMDAR in neurons leads to striping of synaptic contacts and simplification of neuronal cytoarchitecture. Incubation of hippocampal neuron cultures with traxoprodil (4 Nm), arcaine (4 μM) or DFMO (5 μM) reversed the deleterious effects of Aβ25-35 on dendritic spine number and spine morphology. We also evaluated the involvement of A-type K+ currents on the Aβ25-35-induced memory impairment. Administration of Tx3-1 (3 100 pmol/site), a selective IA blocker, restored memory of mice injected with Aβ25-35 and tested on the novel object recognition task The reversal of memory impairment and the protective effect on dendritic spine alterations exerted by the modulators of the polyamine system suggest the polyamine binding site at extrasynaptic NMDAR a potential player in Aβ-induced cognitive deficit.
O peptídeo β-amiloide (Aβ), reconhecido como agente tóxico na Doença de Alzheimer (DA) é implicado como causador de danos cognitivos e sinápticos, apesar de os mecanismos não serem completamente compreendidos. O envolvimento do receptor N-metil-D-aspartato (NMDA) na DA é sugerido, visto que o seu bloqueio atenua alguns aspectos neuropatológicos da DA. Nesse contexto, tem sido demonstrado que as poliaminas, como espermidina e espermina, moduladores positivos do receptor NMDA, possuem níveis e síntese elevada tanto no cérebro de pacientes com DA como em preparações in vitro utilizando o peptídeo Aβ. Neste estudo demonstrou-se que a modulação do sistema das poliaminas, através do bloqueio do seu sítio de ligação no receptor NMDA por arcaína (0,02 nmol/sítio), traxoprodil (0,002 nmol/sítio) ou da inibição de sua síntese por DFMO (2,7 nmol/sítio), reverte o déficit cognitivo induzido pela injeção de Aβ25-35 em camundongos testados na tarefa de reconhecimento de objetos. A ativação do sítio de ligação das poliaminas em receptores NMDA extrassinápticos pode subjazer o déficit cognitivo de camundongos injetados com Aβ25-35, visto que a incubação de culturas primárias de neurônios hipocampais com espermidina (400 μM), NMDA (200 μM) ou Aβ25-35 (10 μM) aumenta o acúmulo nuclear de jacob, um marcador de ativação de receptores NMDA extrassinápticos, de maneira significante. Ademais, traxoprodil (4 nM), arcaína (4 μM) ou DFMO (5 μM) bloquearam o acúmulo nuclear de jacob induzido por Aβ. A ativação de receptores NMDA extrassinápticos em neurônios leva a simplificação da citoarquitetura neuronal e a diminuição de contatos sinápticos. Aqui demonstrou-se que a incubação de culturas de neurônios hipocampais com traxoprodil (4 nM), arcaína (4 μM) ou DFMO (5 μM) reverte as alterações na a densidade e morfologia de espinhas dendríticas induzido pela incubação com Aβ25-35. Ainda, também avaliou-se o envolvimento de correntes de K+ do tipo A no déficit cognitivo induzido pela injeção i.c.v. de Aβ25-35. A administração de Tx3-1 (3 100 pmol/sítio), um bloqueador seletivo de correntes IA, reverteu o prejuízo de memória de camundongos injetados com Aβ25-35 e testados na tarefa de reconhecimento de objetos. A reversão dos danos cognitivos e sinápticos induzidos por Aβ25-35 através da modulação do sistema das poliaminas sugere a estimulação do sítio de ligação das poliaminas no receptor NMDA, possivelmente extrassínaptico, como um dos mecanimos por trás do déficit cognitivo induzido pelo peptídeo Aβ.
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Robertson, Katie E. "Boldness Behavior and Chronic Stress in Free-Ranging, Urban Coyotes (Canis latrans)." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1543529587211372.
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Cole, Emily. "A new test of object-recognition memory for rats." Thesis, 2012. http://spectrum.library.concordia.ca/974781/1/COLE_MA_F2012.pdf.
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Object-recognition memory has been assessed in rats using the delayed non-matching-to-sample (DNMS) task and the novel-object preference (NOP) test. The DNMS task provides an accurate measure of rats’ object-recognition abilities, however, the conventional procedures are not practical because rats require extensive training to reach peak performance and object-recognition memory can only be assessed using retention intervals of up to a few minutes. The NOP test does not require rats to be trained in advance, and for this reason it has become widely popular as a test of object-recognition memory. Recent findings, however, question the internal validity of the NOP test, namely its assumption that the strength of novelty preference corresponds directly to the strength of the memory for an object. The goal of the present study was to develop a new test of object-recognition memory. The new method incorporates the appetitive-reward and explicit choice aspects of the DNMS task and it employs a circular-track apparatus that has been previously used in a modified NOP test. Rats’ performance on the new task was similar to the levels of accuracy reported on conventional DNMS tasks but were achieved in far fewer trials than conventional DNMS tasks. When the delay was increased, performance decreased slightly but remained significantly above chance. Additionally, we compared rats’ performance on the new task to their scores on the NOP test and did not find a consistent linear relationship. The results from this new task confirm its utility as a test of object-recognition memory in rats, while challenging the assumption that the strength of novelty preference on the NOP test corresponds to the strength of memory for an object.
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Verbeke, Aynsley K. "Does performance on the ABLA test predict object name recognition?" 2005. http://hdl.handle.net/1993/20640.
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McLean, Samantha L., Ben Grayson, M. Harris, C. Protheroe, S. Bate, M. L. Woolley, and Joanna C. Neill. "Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats." 2008. http://hdl.handle.net/10454/8486.
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YesIt has been suggested that the isolation rearing paradigm models certain aspects of schizophrenia symptomatology. This study aimed to investigate whether isolation rearing impairs rats’ performance in two models of cognition: the novel object recognition (NOR) and attentional set-shifting tasks, tests of episodic memory and executive function, respectively. Two cohorts of female Hooded-Lister rats were used in these experiments. Animals were housed in social isolation or in groups of five from weaning, post-natal day 28. The first cohort was tested in the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second cohort was trained and tested in the attentional set-shifting task. In the NOR test, isolates were only able to discriminate between the novel and familiar objects up to 1-h ITI, whereas socially reared animals remembered the familiar object up to a 4-h ITI. In the attentional set-shifting task, isolates were significantly and selectively impaired in the extra-dimensional shift phase of the task (P < 0.01). Rats reared in isolation show impaired episodic memory in the NOR task and reduced ability to shift attention between stimulus dimensions in the attentional set-shifting task. Because schizophrenic patients show similar deficits in performance in these cognitive domains, these data further support isolation rearing as a putative preclinical model of the cognitive deficits associated with schizophrenia.
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Muha, V., Ritchie Williamson, R. Hills, A. D. McNeilly, T. G. McWilliams, J. Alonso, M. Schimpl, et al. "Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice." 2019. http://hdl.handle.net/10454/17525.
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YesO-GlcNAcylation is an abundant post-translational modification in the nervous system, linked to both neurodevelopmental and neurodegenerative disease. However, the mechanistic links between these phenotypes and site-specific O-GlcNAcylation remain largely unexplored. Here, we show that Ser517 O-GlcNAcylation of the microtubule-binding protein Collapsin Response Mediator Protein-2 (CRMP2) increases with age. By generating and characterizing a Crmp2S517A knock-in mouse model, we demonstrate that loss of O-GlcNAcylation leads to a small decrease in body weight and mild memory impairment, suggesting that Ser517 O-GlcNAcylation has a small but detectable impact on mouse physiology and cognitive function.
a Wellcome Trust Senior Research Fellowship (WT087590MA) to D.M.F.v.A., an ARUK Pilot Project grant to R.W., and support from Tenovus Scotland to V.M. The phosphoproteomics mass spectrometry work was supported by the Horizon 2020 program INFRAIA project Epic-XS (project 823839) to A.J.R.H.
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Chang, Pi Kai, and 張皕凱. "Effect of dopamine D3 receptor blockade on hyper-dopamine activity-induced deficit in novel object recognition memory." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/j6kgtw.
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博士長庚大學
生物醫學研究所
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Over-activation of dopamine signaling is thought to underlie the pathophysiology of a number of psychiatric disorders, such as psychosis, mania and attention-deficit/hyperactivity disorder (ADHD). These mood disorders are frequently associated with cognitive deficits such as disturbance in attention processes or learning and memory, suggesting that persistent changes in dopamine signaling may alter neural plasticity and lead to disease progress. In order to model overactive DA transmission in a well-established novel object recognition (NOR) memory test, we used DA transporter knockdown (DAT-KD) mice, which exhibit reduced DAT expression and display hyper-dopaminergic phenotypes. DAT-KD mice exhibited impaired NOR memory compared to wild-type (WT) mice. This impairment was prevented by administration of FAUC365, a DA D3 receptor (D3R) selective antagonist, prior to object learning. Similarly, D3R knockout (KO)/DAT-KD double mutant mice displayed comparable performance in the NOR test as to WT mice, suggesting that deficiencies in NOR performance in DAT-KD mice can be compensated by diminishing D3R signaling. GBR12909, a DAT blocker, also impaired NOR performance in WT mice, but not in D3R KO mice. Impaired NOR performance in GBR12909-treated WT mice was also prevented by pretreatment with FAUC365. To search underlying signaling, levels of p-GSK3α and p-GSK3β in the mPFC of WT mice were significantly decreased after exposure to the novel objects. On the contrary, DAT-KD mice did not exhibit change in levels of mPFC p-GSK3alpha/beta, but treatment of FAUC365 or D3 deletion restored the novelty-induced dephosphorylation in the mPFC of DAT-KD mice. In this context, inhibition of GSK3 activity or knockdown of GSK3beta disrupted NORT in WT mice. Together, these findings indicate that reduced DAT activity can impair recognition memory in the NOR test and appears to link with a disruption of D3 receptor-dependent GSK3beta signaling in the mPFC during memory encoding, hence fails to recognize the novel object in test session.
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Ingelman, Åslund Trollet. "Beteendesyndrom hos blankål (Anguilla anguilla): aktivitet och respons på främmande objekt i en artificiell miljö." Thesis, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-78803.
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Ökad kunskap om djurs beteendesyndrom kan möjliggöra förbättrade bevarandeåtgärder för hotade arter. I den här studien genomgick 108 blankålar (Anguilla anguilla) två beteendetester; “open-field test” och “novel-object test”. Ålars morfologi och val av föda, habitat och dygnsaktivitet har i tidigare studier visats hänga ihop. I den här studien undersökte jag om det fanns något samband mellan ålarnas morfologi, aktivitet samt respons på främmande föremål. De ålar som var mest aktiva under open-field-testet var också de ålar som visade störst intresse för det främmande föremålet i novel-object-testet. Det fanns dock inte något samband mellan morfologi och aktivitet eller mellan morfologi och respons på främmande föremål. Detta innebär att ett utforskande och djärvt beteendesyndrom har upptäckts hos vissa av ålarna, medan den bakomliggande faktorn fortsätter vara okänd.Increased knowledge of behavioural syndromes may contribute to enhancing our conservation methods for endangered species. In this study, the behavior of 108 silver eels (Anguilla anguilla) was assessed in two assays: an open-field test and a novel-object test. Eel morphology and diel activity as well as diet and habitat use have previously been shown to correlate with each other. In this study, I investigated the potential relationship between the morphology, activity and response to a novel object. The most active eels during the open-field test were also the ones that expressed the most interest for the novel object. There was, however, no correlation between morphology and activity or morphology and response to the novel object. This means an exploring and bold behaviour syndrome was discovered amongst some of the eels, whilst the underlying cause remains unknown.
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Janetsian-Fritz, Sarine S. "Early-life trauma alters hippocampal function during an episodic memory task in adulthood." Thesis, 2017. https://doi.org/10.7912/C2WM0Q.
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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.
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Watremez, W., J. Jackson, B. Almari, Samantha L. McLean, B. Grayson, J. C. Neilla, N. Fischer, et al. "Stabilized low-n amyloid-ß oligomers induce robust novel object recognition deficits associated with inflammatory, synaptic, and GABAergic dysfunction in the rat." 2017. http://hdl.handle.net/10454/15087.
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YesBackground:With current treatments for Alzheimer’s disease (AD) only providing temporary symptomatic benefits, disease modifying drugs are urgently required. This approach relies on improved understanding of the early pathophysiology of AD. A new hypothesis has emerged, in which early memory loss is considered a synapse failure caused by soluble amyloid-β oligomers (Aβo). These small soluble Aβo, which precede the formation of larger fibrillar assemblies, may be the main cause of early AD pathologies. Objective:The aim of the current study was to investigate the effect of acute administration of stabilized low-n amyloid-β1-42 oligomers (Aβo1-42) on cognitive, inflammatory, synaptic, and neuronal markers in the rat. Methods:Female and male Lister Hooded rats received acute intracerebroventricular (ICV) administration of either vehicle or 5 nmol of Aβo1-42 (10μL). Cognition was assessed in the novel object recognition (NOR) paradigm at different time points. Levels of inflammatory (IL-1β, IL-6, TNF-α), synaptic (PSD-95, SNAP-25), and neuronal (n-acetylaspartate, parvalbumin-positive cells) markers were investigated in different brain regions (prefrontal and frontal cortex, striatum, dorsal and ventral hippocampus). Results:Acute ICV administration of Aβo1-42 induced robust and enduring NOR deficits. These deficits were reversed by acute administration of donepezil and rolipram but not risperidone. Postmortem analysis revealed an increase in inflammatory markers, a decrease in synaptic markers and parvalbumin containing interneurons in the frontal cortex, with no evidence of widespread neuronal loss. Conclusion:Taken together the results suggest that acute administration of soluble low-n Aβo may be a useful model to study the early mechanisms involved in AD and provide us with a platform for testing novel therapeutic approaches that target the early underlying synaptic pathology.
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McLean, Samantha L., Haesung Yun, Andrew Tedder, and Gisela Helfer. "The effect of photoperiod and high fat diet on the cognitive response in photoperiod-sensitive F344 rats." 2021. http://hdl.handle.net/10454/18550.
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noIn many species, seasonal changes in day length (photoperiod) have profound effects on physiology and behavior. In humans, these include cognitive function and mood. Here we investigated the effect of photoperiod and high fat diets on cognitive deficits, as measured by novel object recognition, in the photoperiod-sensitive F344 rat, which exhibits marked natural changes in growth, body weight and food intake in response to photoperiod. 32 male juvenile F344 rats were housed in either long or short photoperiod and fed either a high fat or nutrient-matched chow diet. Rats were tested in the novel object recognition test before photoperiod and diet intervention and re-tested 28 days after intervention. In both tests during the acquisition trials there was no significant difference in exploration levels of the left and right objects in the groups. Before intervention, all groups showed a significant increase in exploration of the novel object compared to the familiar object. However, following the photoperiod and diet interventions the retention trial revealed that only rats in the long photoperiod-chow group explored the novel object significantly more than the familiar object, whereas all other groups showed no significant preference. These results suggest that changing rats to short photoperiod impairs their memory regardless of diet. The cognitive performance of rats on long photoperiod-chow remained intact, whereas the high fat diet in the long photoperiod group induced a memory impairment. These findings suggest that rats exposed to long photoperiod have different cognitive responses to rats exposed to short photoperiod and high fat diet.
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McLean, Samantha L., Ben Grayson, Nagi F. Idris, A. S. Lesage, D. J. Pemberton, C. Mackie, and Joanna C. Neill. "Activation of α7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: Implications for therapy of cognitive dysfunction in schizophrenia." 2010. http://hdl.handle.net/10454/8464.
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YesRationale: Nicotinic α7 acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Aim: To investigate whether the deficits induced by sub-chronic phencyclidine (PCP) in reversal learning and novel object recognition could be attenuated by the selective α7 nAChR full agonist, PNU-282987. Methods: Adult female hooded-Lister rats received sub-chronic PCP (2 mg/kg) or vehicle i.p. twice daily for seven days, followed by 7-days washout. In cohort 1, PCP-treated rats then received PNU-282987 (5, 10, 20 mg/kg; s.c.) or vehicle and were tested in the reversal learning task. In cohort 2, PCP-treated rats received PNU-282987 (10 mg/kg; s.c.) or saline for 15 days and were tested in the novel object recognition test on day 1 and on day 15, to test for tolerance. Results: Sub-chronic PCP produced significant deficits in both cognitive tasks (P<0.01-0.001). PNU-282987 attenuated the PCP-induced deficits in reversal learning at 10 mg/kg (P<0.01) and 20 mg/kg (P<0.001), and in novel object recognition at 10 mg/kg on day 1 (P<0.01) and on day 15 (P<0.001). Conclusions: These data show that PNU-282987 has efficacy to reverse PCP-induced deficits in two paradigms of relevance to schizophrenia. Results further suggest that 15 day daily dosing of PNU-282987 (10 mg/kg s.c.) does not cause tolerance in rat. This study suggests that activation of α7 nAChRs, may represent a suitable strategy for improving cognitive deficits of relevance to schizophrenia.
SL McLean was supported by a joint University of Bradford–GSK postgraduate studentship.
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Bloch, Sherri. "Exploration of the Cerebral Dysfunctions Induced by Arterial Rigidity and/or the Overexpression of TGFβ in a Mouse Model." Thèse, 2017. http://hdl.handle.net/1866/20528.
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