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In order to investigate if difference in personality is depended on the teat positions in piglets, Sus scrofa, 63 piglets, from 21 litters, were studied. The piglets were at an age between 9 and 31 days. 3 piglets in each of the 21 litters, one that suckled at an anterior teat, one at a middle teat, and one at a posterior teat, were studied during lactation, undisturbed activity, and introduction to a novel object respectively to new straw. In total thirteen behaviors were recorded. The only significant difference between the teat position were disputes during suckling (P=0.018). There was a tendency of playing during undisturbed activity (P=0.062) between the teat positions. There were significant differences between the litters for every behavior except for inactive piglet lying alone (P=0.108) and when exploring new straw (P=0.584). There is only evidence for behavioral differences for the frequency of disputes during suckling between piglets at different teat positions. A principal component analysis, which accounted for 64.2 % of the variance, suggested four personality traits: exploration (19.2 %), playfulness (17.5 %), interest in food (14.8 %), and interest in straw (10.9 %). However, no significant differences were found for these components for the different teat positions.

Research where personality in animals is studied is becoming more and more common. In this area there are different concepts like behavioural syndrome and animal personality and they usually talk about consistency in behaviour over time and situations. This consistent individual behaviour can be used as an indicator of how individuals can handle and adjust to new situations in the environment. Because of this, personality studies in animals are very important in animal welfare. In this study personality in dairy cattle in lose housing were studied. 28 cows of the breeds Swedish black and white cattle (SLB) and Swedish red and white cattle (SRB) was studied during three observation situations (milking, undisturbed behaviour and novel object). With the help of Principal component analysis four components that together explained 72% of the variation in data were found. The two first components could then be interpreted. The first component corresponds to the dimension extraversion in the”Big five” model that is used in personality studies in humans. The second component was the opposite of the first one, which means that it showed low activity and low sociability. This low activity could indicate fear dependent on why the cows were standing so much. T-tests only showed significant differences in the behaviour based on the age of the cows, which indicates that the personality trait becomes more typical with higher age. The conclusion is that there are individual differences in dairy cattle which could be interpreted as personality traits.

Variation in animal personality, in other words, behavioural responses consistent within individuals over time and/or across contexts, is predicted to be related to life-history traits, such as growth rate and investment in reproduction. How this translates into relationships between personality and milk production in dairy cows is however scarcely investigated and previous studies are showing contradicting results. To further investigate this relationship, individual consistencies in behaviour were related to milk production in two breeds of dairy cows (Swedish red and white cattle, SRB, and Holstein). Variation was found among the breeds in consistency of behaviours and both SRB and Holstein cows were highly consistent over time in stepping behaviour during milking and frequency of performed abnormal behaviours in home pen. Overall were Holstein cows consistent in more observed behaviours than SRB. Variation in neophobia and responses to social separation were more flexible, both among breeds and over time. Nevertheless, behaviour showed limited relationship with milk production. To conclude, the tests here carried out are useful in describing personality in cows; however, personality showed no relationship with milk production, encouraging future studies to explore this expected relationship further in other breeds and species.

To investigate whether piglets show different personality types due to teat position, a number ofexperiments were performed on 21 different litters, 9 to 31 days old. The tests included threefocal piglets in each litter with different teat position, anterior, middle and posterior, inobservations on suckling behaviour, undisturbed behaviours, a novel object test and a straw-testwhere thirteen behaviours were observed. The tests found an effect on teat position on frequencyof disputes between piglets during suckling and their teat position (P=0.018) and a tendency ofdifference in undisturbed playing behaviour between piglets at different teat position (P=0.057).All tests found differences between litters concerning behaviours. With a Principal componentanalysis, the four personality types curiosity, playful, food interest and straw interest wasestablished. No effect between different teat positions and personality type were found, but atendency of difference between personality trait playful and different teat positions (P=0.062). Inconclusion: no significant differences between teat position and personality type in piglets couldbe established.

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.

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.

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.

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.

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.