Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O uso combinado de etanol e bebidas energéticas tem aumentado entre adolescentes. Além disso, estudos epidemiológicos indicam que o co-uso aumenta a probabilidade de consumo abusivo e dependência de etanol. Apesar disso, pouco se sabe sobre as consequências neurocomportamentais da co-exposição no cérebro adolescente. Este estudo tem como objetivo avaliar o curso temporal dos efeitos agudos da exposição à bebida energética e/ou etanol na atividade motora e ansiedade no teste de campo aberto, como também, os efeitos agudos ou prolongados sobre aprendizagem/memória e coordenação motora em camundongos adolescentes. Camundongos Suíços foram divididos em 4 grupos: bebidas energéticas e etanol, bebida energética, etanol e água. Três estudos separados foram conduzidos para avaliar cada um dos objetivos específicos deste trabalho. No primeiro estudo, realizado em PN40, os animais receberam a administração de bebida energética (8 ml/kg) e/ou etanol (4 g/kg) por gavagem e após 55 minutos foram submetidos ao teste do campo aberto (sessão 1). Outras duas sessões foram realizadas em sequência usando a metade da dose inicial (sessão 2 e 3). Nos estudos 2 e 3, estudamos os efeitos agudos (PN40) e crônicos (exposição de PN30-40) sobre o teste de esquiva passiva (0,3 mA, 3 s) e sobre o desempenho no teste do cilíndro giratório (sessão de treinamento e após 1 e 3 horas da gavagem das drogas). Em ambos os casos, a dose de bebida energética (8 ml/kg) e/ou etanol (4 g/kg) foi administrada. No teste da esquiva passiva, as sessões de treino e retenção foram realizadas 1 e 24 horas após a administração da droga, respectivamente. No teste do Rotarod, cada sessão foi constituída por 5 tentativas em modelo de aceleramento contínuo (4 a 40 rpm/min em uma tentativa de 2 min). Os nossos dados indicam que a exposição concomitante a bebida energética potencializa o efeito de hiperatividade induzido pelo etanol, como também, gera uma resposta ansiogênica no teste do campo aberto. A exposição aguda ao etanol induz déficit de memória/aprendizagem que não é revertida pela BE. A co-exposição aguda a bebida energética e etanol prolongou incoordenação motora induzida pelo etanol. No entanto, a bebda energética reverteu o comprometimento da coordenação motora gerada pela exposição crônica de etanol em camundongos fêmeas. O presente estudo fornece evidência experimental de que bebida energética e etanol interagem durante a adolescência, resultando em padrões de comportamento que poderiam aumentar o risco de desenvolvimento de abuso ou dependência de etanol. Além disso, os dados indicaram que a exposição aguda à bebida energética não atenuou as consequências negativas geradas pela etanol no desempenho do motor e cognitivo. / The combined use of ethanol and energy drinks has increased among adolescents. Furthermore, epidemiological studies indicate that the co-use increases the likelihood of abuse and ethanol dependence. Nevertheless, little is known about the neurobehavioral effects of co-exposure in adolescent brain. This study aims to evaluate the time course of the acute effects of exposure to energy drink and / or ethanol in motor activity and anxiety in the open field test, but also acute or prolonged effects on learning/memory and motor coordination in mice teens. Swiss mice were divided into 4 groups: ethanol and energy drinks, energy drinks, ethanol and water. Three separate studies were conducted to evaluate each of the specific objectives of this work. In the first study, conducted in PN40, animals received the energy drink administration (8 ml/kg) and / or ethanol (4 g/kg) by gavage and after 55 minutes were subjected to the open field test (session 1). Other two sessions were conducted in sequence using half of the initial dose (session 2 and 3). In trials 2 and 3, we studied the acute effects (PN40) and chronic (exposure PN30-40) on the passive avoidance test (0.3 mA, 3s) and the test performance of the rotary cylinder (training session and 1 and 3 hours after the gavage of drugs). In both cases, the dose of energy drink (8 ml/kg) and / or ethanol (4 g/kg) was administered. In the test of passive avoidance training sessions and the retention were made 1 and 24 hours after drug administration, respectively. In the Rotarod test, each session consisted of 5 trials continuous acceleration model (4 to 40 rpm / min in an attempt to 2 min). Our data indicate that the concurrent exposure to energy drink enhances the effect hyperactivity induced by ethanol, as also, it generates an anxiogenic response in the Open Field test. Acute ethanol exposure induces memory/learning deficits that is not reversed by BE. Acute co-exposure to energy drink and ethanol prolonged incoordination induced by ethanol. However, energy drink reversed the impairment of motor coordination generated by chronic exposure of ethanol in female mice. This study provides experimental evidence that energy drink and ethanol interact during adolescence, resulting in behavioral patterns that could increase the risk of abuse or dependence on ethanol. In addition, the data indicated that acute exposure to energy drink did not attenuate the negative consequences generated by ethanol in motor performance and cognitive.

This research project examined the role of environmental time cues and circadian rhythms in mediating seasonal adjustments in the body temperature and locomotoractivity patterns in the Australian sleepy lizard, Tiliqua rugosa (Gray 1827). The first component of this study investigated whether daily rhythms of behavioural thermoregulation and locomotor activity that T. rugosa displays in the field are endogenous circadian rhythms. In each season, there was significant variation in each of these rhythms in lizards released on laboratory thermal gradients under prevailing light-dark (LD) cycles. Both rhythms persisted when lizards were released in constant darkness (DD) and exhibited the same free-running period suggesting a single circadian pacemaker drives both rhythms. The first component of this study revealed that seasonal changes in the expression of daily behavioural thermoregulatory and locomotor activity rhythms are mediated by the circadian system in T. rugosa. The second component of this project comprised three experiments that determined the relative importance of 24 h LD and temperature cycles (TCs) in entraining the locomotor activity rhythm. In the first experiment, lizards were held under LD 12:12 and were subjected to either a TC of 33:15C in phase with the LD cycle or a reversed TC. Following LD 12:12, lizards were maintained under the same TCs but were subjected to DD. Activity was restricted to the thermophase in LD irrespective of the lighting regime and during the period of DD that followed, suggesting entrainment by the TC. In the second experiment, lizards were held under LD 12.5:11.5 and were subjected to one of three treatments; (1) constant 30C, (2) normal TC (30:20C), or (3) reversed TC. Following LD, all lizards were subjected to DD and constant 30C. Post-entrainment free-run records revealed that LD cycles and TCs both entrain locomotor activity rhythms of T. rugosa. Although there was large variation in the phasing of the rhythm in relation to the LD cycle in reversed TC lizards, TCs presented in phase with the LD cycle most accurately synchronised the rhythm to the photocycle. In the third experiment, lizards were held in DD at constant 30C before being subjected to a further period of DD and one of four treatments; (1) normal TC (06:00 h to 18:00 h thermophase), (2) delayed TC (12:00 h to 00:00 h thermophase), (3) advanced TC (00:00 h to 12:00 h thermophase) or (4) control (no TC, constant 30C). While control lizards continued to free-run in DD at constant temperature, locomotor rhythms of lizards subjected to TCs rapidly entrained to TCs irrespective of whether TCs were phase advanced or delayed by 6 h. The results of this experiment excluded the possibility that masking effects were responsible for locomotor responses of lizards to TCs. This study demonstrated that seasonal changes in the expression of this species‟ daily behavioural thermoregulatory and locomotor rhythms are mediated by a circadian system that is sensitive to both light and temperature. The sensitivity of the circadian system to temperature, in particular, may allow T. rugosa to restrict its activity to times of the year that are thermally favourable. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1521959 / Thesis(Ph.D.)-- University of Adelaide, School of Medical Sciences, 2010

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O uso combinado de etanol e bebidas energéticas tem aumentado entre adolescentes. Além disso, estudos epidemiológicos indicam que o co-uso aumenta a probabilidade de consumo abusivo e dependência de etanol. Apesar disso, pouco se sabe sobre as consequências neurocomportamentais da co-exposição no cérebro adolescente. Este estudo tem como objetivo avaliar o curso temporal dos efeitos agudos da exposição à bebida energética e/ou etanol na atividade motora e ansiedade no teste de campo aberto, como também, os efeitos agudos ou prolongados sobre aprendizagem/memória e coordenação motora em camundongos adolescentes. Camundongos Suíços foram divididos em 4 grupos: bebidas energéticas e etanol, bebida energética, etanol e água. Três estudos separados foram conduzidos para avaliar cada um dos objetivos específicos deste trabalho. No primeiro estudo, realizado em PN40, os animais receberam a administração de bebida energética (8 ml/kg) e/ou etanol (4 g/kg) por gavagem e após 55 minutos foram submetidos ao teste do campo aberto (sessão 1). Outras duas sessões foram realizadas em sequência usando a metade da dose inicial (sessão 2 e 3). Nos estudos 2 e 3, estudamos os efeitos agudos (PN40) e crônicos (exposição de PN30-40) sobre o teste de esquiva passiva (0,3 mA, 3 s) e sobre o desempenho no teste do cilíndro giratório (sessão de treinamento e após 1 e 3 horas da gavagem das drogas). Em ambos os casos, a dose de bebida energética (8 ml/kg) e/ou etanol (4 g/kg) foi administrada. No teste da esquiva passiva, as sessões de treino e retenção foram realizadas 1 e 24 horas após a administração da droga, respectivamente. No teste do Rotarod, cada sessão foi constituída por 5 tentativas em modelo de aceleramento contínuo (4 a 40 rpm/min em uma tentativa de 2 min). Os nossos dados indicam que a exposição concomitante a bebida energética potencializa o efeito de hiperatividade induzido pelo etanol, como também, gera uma resposta ansiogênica no teste do campo aberto. A exposição aguda ao etanol induz déficit de memória/aprendizagem que não é revertida pela BE. A co-exposição aguda a bebida energética e etanol prolongou incoordenação motora induzida pelo etanol. No entanto, a bebda energética reverteu o comprometimento da coordenação motora gerada pela exposição crônica de etanol em camundongos fêmeas. O presente estudo fornece evidência experimental de que bebida energética e etanol interagem durante a adolescência, resultando em padrões de comportamento que poderiam aumentar o risco de desenvolvimento de abuso ou dependência de etanol. Além disso, os dados indicaram que a exposição aguda à bebida energética não atenuou as consequências negativas geradas pela etanol no desempenho do motor e cognitivo. / The combined use of ethanol and energy drinks has increased among adolescents. Furthermore, epidemiological studies indicate that the co-use increases the likelihood of abuse and ethanol dependence. Nevertheless, little is known about the neurobehavioral effects of co-exposure in adolescent brain. This study aims to evaluate the time course of the acute effects of exposure to energy drink and / or ethanol in motor activity and anxiety in the open field test, but also acute or prolonged effects on learning/memory and motor coordination in mice teens. Swiss mice were divided into 4 groups: ethanol and energy drinks, energy drinks, ethanol and water. Three separate studies were conducted to evaluate each of the specific objectives of this work. In the first study, conducted in PN40, animals received the energy drink administration (8 ml/kg) and / or ethanol (4 g/kg) by gavage and after 55 minutes were subjected to the open field test (session 1). Other two sessions were conducted in sequence using half of the initial dose (session 2 and 3). In trials 2 and 3, we studied the acute effects (PN40) and chronic (exposure PN30-40) on the passive avoidance test (0.3 mA, 3s) and the test performance of the rotary cylinder (training session and 1 and 3 hours after the gavage of drugs). In both cases, the dose of energy drink (8 ml/kg) and / or ethanol (4 g/kg) was administered. In the test of passive avoidance training sessions and the retention were made 1 and 24 hours after drug administration, respectively. In the Rotarod test, each session consisted of 5 trials continuous acceleration model (4 to 40 rpm / min in an attempt to 2 min). Our data indicate that the concurrent exposure to energy drink enhances the effect hyperactivity induced by ethanol, as also, it generates an anxiogenic response in the Open Field test. Acute ethanol exposure induces memory/learning deficits that is not reversed by BE. Acute co-exposure to energy drink and ethanol prolonged incoordination induced by ethanol. However, energy drink reversed the impairment of motor coordination generated by chronic exposure of ethanol in female mice. This study provides experimental evidence that energy drink and ethanol interact during adolescence, resulting in behavioral patterns that could increase the risk of abuse or dependence on ethanol. In addition, the data indicated that acute exposure to energy drink did not attenuate the negative consequences generated by ethanol in motor performance and cognitive.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Abnormal movements are clinical symptoms present in neurodegenerative diseases, such Parkinsonism , as well as Tardive dyskinesia. It is thought that unbalance in monoamine levels with their consequent metabolism could be involved in the etiology of these abnormal movements. However, until this moment there is not efficacious treatment with low side effects for these conditions. In this context, Hypericum perforatum (H. perforatum), popularly known as St. John s Wort, is a plant largely used as antidepressant and presenting high amount of polyphenol constituents. Its antidepressant mechanism seems to involve the increase of monoamines and monoaminoxidase inhibition. Here, we evaluated the effect of H. perforatum on different models of abnormal movements in rats, either using fluphenazine or reserpine. It were quantified the number of vacuous chewing movements (VCMs) and locomotor activity (number or rearings and crossings) in both models. In experiment 1, rats received a single administration of fluphenazine enantate (25 mg/Kg, i.m.) and/or H. perforatum (300 mg/Kg, in place of drinking water) during 7 days. Fluphenazine treatment increased VCMs and decreased the locomotor activity after 7 days of treatment. However, H. perforatum did not alter either the number of VCMs or the locomotor activity (represented by number of crossing and rearing in the open field test) in rats. In experiment 2, rats received reserpine administration once a day during 3 days (0.5 mg/Kg, s.c.) and/or H. perforatum (300 mg/Kg, in place of drinking water) during 16 days. Reserpine treatment increased VCMs and decreased the locomotor activity. H. perforatum did not alter the number of VCMs or the number of rearing. However, H. perforatum co-treatment could avoid the effect of reserpine on number of crossings. In conclusion, H. perforatum did not seem to be efficacious to protect against orofacial movements induced by fluphenazine or reserpine in rats. / As desordens motoras são sintomas de doenças neurodegenerativas bem como podem estar associadas ao tratamento com antipsicóticos. Cita-se como exemplo destas desordens, sintomas da Doença de Parkinson (DP) e a Discinesia Tardia (DT), respectivamente. O desequilíbrio cerebral nos níveis de monoaminas e, consequentemente, seu metabolismo tem sido relacionados ao desenvolvimento dos movimentos anormais que aparecem nas desordens motoras, tendo em vista que os circuitos dopaminérgicos estão envolvidos na gênese da DP e da DT. No entanto, ainda não existem tratamentos eficazes e com poucos efeitos colaterais para tais condições. A Hypericum perforatum (H. perforatum), popularmente conhecido como Erva de São João, consiste numa planta amplamente utilizada como antidepressiva e que possui uma grande quantidade de compostos fenólicos, cujo mecanismo para esta atividade está relacionado à inibição da monoamina oxidade (MAO) e da recaptação de monoaminas cerebrais. Assim, o objetivo do presente estudo foi investigar o efeito do H. perforatum em modelos de desordem motora induzida por flufenazina ou reserpina em ratos. Foram quantificados os movimentos de mascar no vazio (MMV) e atividade locomotora (cruzamentos e levantadas observados no teste de campo aberto) em ambos os modelos. No experimento 1, os ratos receberam uma única administração de enantato de flufenazina (25 mg/Kg, i.m.) e ou H. perforatum (300 mg/Kg, no lugar da água de beber) durante 7 dias. O tratamento com flufenazina aumentou o número de MMVs e diminuiu a atividade locomotora em ratos após 7 dias de tratamento. No entanto, o tratamento com H. perforatum não protegeu das alterações comportamentais causadas pelo tratamento com flufenazina. No experimento 2, os ratos receberam água ou H. perforatum (300 mg/Kg, no lugar da água de beber) durante 16 dias. A partir do dia 9 de tratamento os animais receberam uma administração diária de reserpina (0,5 mg/Kg, s.c.) ou veículo durante 3 dias com intervalo de 48 horas. A reserpina aumentou o número MMVs e diminuiu a atividade locomotora em campo aberto. O prétratamento com H. perforatum não alterou o efeito da reserpina sobre o número de MMVs e levantadas. Porém, o pré-tratamento com H. perforatum preveniu o efeito da reserpina sobre número de cruzamentos. Desta forma, podemos concluir que o H. perforatum não apresentou efeito benéfico sobre os movimentos orofaciais induzidos por flufenazina ou reserpina em ratos.

Le système sérotoninergique central a longtemps été associé au contrôle du comportement alimentaire et à la modulation des effets des drogues psychostimulantes sur le comportement.Le récepteur 5-HT2C est présent dans les centres hypothalamiques et particulièrement dans le noyau arqué dans l’hypothalamus (ARC) qui contrôle la régulation homéostatique de la prise alimentaire. On le retrouve aussi dans l’aire tegmentaire ventrale (VTA), une région importante dans la motivation de plusieurs comportements notamment la consommation alimentaire.Dans cette étude, l’hypothèse testée est, d’une part, que le récepteur 5-HT2C exprimé dans le VTA jouerait un rôle dans le contrôle de l’activité locomotrice induite par l’amphétamine et d’autre part qu’il exercerait son effet hypophagique a travers l’ARC.Des micro-injections localisées dans le VTA et dans l’ARC ont été réalisées afin d’évaluer les effets d’un agoniste sélectif du récepteur 5-HT2C, AR231630, sur l’hyperlocomotion stimulée par l’amphétamine ainsi que sur la prise alimentaire chez le rat.Dans les tests sur l’activité locomotrice, AR231630, lorsque qu’injecté dans la VTA, et non pas dans l’ARC, réduit de façon dose-dépendante l’ambulation provoquée par l’amphétamine.Dans les tests sur le comportement alimentaire, l’injection du composé AR231630 dans l’ARC n’induit pas de réduction de la prise alimentaire, contrairement au VTA.Une expérience suivante montre que les effets inhibants de l’administration périphérique d’AR231630 (5mg/kg) sur l’alimentation sont spécifiquement inversés par un prétraitement dans le VTA avec un antagoniste sélectif du récepteur 5-HT2C, SB242084.Ces résultats suggèrent que les récepteurs 5-HT2C dans le VTA participent à la fois au comportement alimentaire et à la fonction de la récompense, et ce, potentiellement par le même mécanisme. / Central serotonin systems have long been associated with the control of ingestive behavior, and the modulation of behavioral effects of psychostimulants.The 5-HT2C receptor is present in hypothalamic centers particularly the arcuate nucleus (ARC) controlling homeostatic regulation of food intake as well as in the ventral tegmental area (VTA), a region important for motivational aspects of multiple behaviors, including feeding.In the present study, the hypothesis was tested that the 5-HT2CR in the VTA may control amphetamine-evoked locomotor activity and 5-HT2CR in the ARC may regulate food consumption. Localized microinjections into the VTA or into the ARC were used to assess the effects of a highly selective 5-HT2C agonist, AR231630, on the locomotor stimulant effect of amphetamine as well as food intake. In the tests for locomotor activity, AR231630 into the VTA, but not into the ARC, dose-dependently reduced locomotor activity elicited by amphetamine. Unexpectedly, in tests for food intake, intra-ARC injection of AR231630 did not reduce food intake even at doses of 10ug, whereas intra-VTA injection of 10ug AR231630 did. A subsequent experiment determined that the suppressant effect of peripheral administration of AR231630 (5 mg/kg) on feeding was partially reversed by pretreatment with the selective 5-HT2CR antagonist SB242084 into the VTA (5ug). These findings suggest that 5-HT2CR in the VTA participates in both food intake and brain reward function, and possibly through the same pathway.

Les soins parentaux sont observés dans de nombreux taxons et sont exprimés de façon plus ou moins complexe. L’étude de ces comportements chez les arthropodes, en particulier chez les araignées, nous permet de mieux comprendre comment les soins à la progéniture se sont mis en place au cours de l’évolution. Au cours de cette thèse nous avons étudié le comportement d’une espèce errante Pardosa saltans (Lycosidae) vis-à-vis de son cocon, puis de ses jeunes. Nous avons décrit les comportements manifestés par la mère pendant toute la période de soin au cocon (période de développement embryonnaire et postembryonnaire des jeunes). Notre étude a permis de mettre en évidence qu’il existe une ontogenèse comportementale dans le cadre des soins parentaux chez cette espèce. Elle a permis également d’évaluer les dépenses énergétiques subies par la mère pendant cette période. Et enfin nous avons identifié, pour la première fois, les composés chimiques présents à la surface du cocon. Nos expériences montrent que ces composés chimiques associés aux vibrations émises par les juvéniles à l’intérieur du cocon sont utilisés par la mère détecter l’état de développement de sa progéniture. / Parental care is widespread among animal kingdom and is more or less expressed. Thus, the study of these behaviours among primitive species, can let us understand how parental behaviours were implemented during evolution. In this thesis we studied maternal behaviour in a wandering spider Pardosa saltans (Lycosidae) with her egg-sac and her young which she actively transports. We have described maternal behaviour towards the egg-sac and highlighted the presence of ontogeny of maternal behavior in this species. Furthermore, we were able to evaluate some of the physiological and ecological investment associated with maternal care of the egg-sac and young. Finally, we have, for the first time, identify chemical compounds on the surface of the silk egg-sac, and placed in evidence the presence of a chemical and vibrational communication between the mother and her cocoon.

Rationale: There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. Objectives: The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption. Methods: The experiments examined the effects of systemic administration of nicotine on locomotor activity, the effects of nicotine administered directly into the (posterior ventral tegmental area; pVTA) on dopamine (DA) release in the nucleus accumbens shell (AcbSh), and innate mRNA levels of acetylcholine receptor genes in the pVTA were determined in 6 selectively bred high/low alcohol consuming and Wistar rat lines. Results: The high alcohol-consuming rat lines had greater nicotine-induced locomotor activity compared to low alcohol-consuming rat lines. Microinjections of nicotine into the pVTA resulted in DA release in the AcbSh with the dose response curves for high alcohol-consuming rats shifted leftward and upward. Genetic analysis of the pVTA indicated P rats expressed higher levels of α2 and β4. Conclusion: Selective breeding for high alcohol preference resulted in a genetically divergent behavioral and neurobiological sensitivity to nicotine. The observed behavioral and neurochemical differences between the rat lines would predict an increased likelihood of nicotine reinforcement. The data support the hypothesis of a common genetic basis for drug addiction and identifies potential receptor targets.

A esquizofrenia é uma desordem neuropsiquiátrica de importância significativa para as pesquisas na área da saúde, porém, apesar de ser alvo de inúmeros estudos clínicos e básicos ainda são levantadas muitas dúvidas a respeito de sua etiologia, fisiopatologia e tratamento. Nos últimos anos, hipóteses que relacionam a esquizofrenia a alterações em sistemas neurotransmissores têm sido bem relevantes. Atualmente a hipótese glutamatérgica complementa a dopaminérgica, já que o bloqueio de receptores glutamatérgicos do tipo NMDA induz sintomas do tipo psicóticos em indivíduos saudáveis e exacerba ou precipita sintomas da esquizofrenia em indivíduos portadores da doença, sugerindo que um estado hipofuncional desses receptores possa causar alterações secundárias em outros sistemas neurotransmissores e provocar tanto os sintomas positivos e negativos quanto os déficits cognitivos da doença. O canabidiol (CBD) é um composto derivado da Cannabis sativa que não apresenta os efeitos psicotomiméticos e os sintomas colaterais geralmente provocados pela utilização da planta e que são, em sua maioria, atribuídos ao delta-9-tetrahidrocanabinol (THC). Recentemente os estudos a respeito da participação do sistema endocanabinóide em diversos estados fisiológicos e, também em transtornos psiquiátricos, apontam o uso terapêutico de canabinóides como uma estratégia promissora para o controle e prevenção de alguns sintomas ligados a transtornos psicóticos. O perfil antipsicótico do CBD já foi comprovado em modelos experimentais e até em análises clínicas, indicando que esse composto é capaz de prevenir estados psicóticos transitórios, provocados tanto pelo THC quanto pela ketamina, em modelos de psicose induzida. O objetivo deste trabalho foi incrementar as informações já existentes sobre o perfil antipsicótico proposto para o CBD, porém, em três tipos de tarefas comportamentais em roedores, que representam três classes de sintomas do tipo psicóticos que se assemelham aos sintomas da esquizofrenia: atividade locomotora, inibição pré-pulso do reflexo de sobressalto (PPI) e teste de interação social. No modelo utilizado, a S(+)-ketamina (KET) é eficaz na indução de comportamentos que representem sintomas do tipo psicóticos - provocou hiperlocomoção, déficit no filtro sensório-motor e prejuízo no comportamento social. Esses são foram reduzidos quando realizado pré-tratamento com clozapina, com exceção do teste de interação social. Os efeitos do CBD são de acordo com o que é descrito na literatura, apresentando uma curva em U farmacológica característica e diferentes efeitos 6 de acordo com a dose empregada. A análise no monitor de atividades indica que o pré- tratamento com CBD na dose de 30 mg/kg previne a hiperlocomoção induzida por KET, contrastando com o pré-tratamento com CBD na dose de 60 mg/kg, que provoca o aumento do comportamento exploratório após a administração de KET. No PPI, o CBD na dose de 30 mg/kg previne o déficit provocado pela administração de KET, demonstrando-se eficaz para o tratamento de prejuízos cognitivos que acompanham as psicoses; e aumenta o reflexo de sobressalto quando associado a KET. Porém, no teste de interação social, não foram detectadas diferenças significativas. Portanto, com esses resultados, demonstrou-se que o CBD pode ser realmente efetivo para o tratamento de determinados sintomas dos transtornos psicóticos, assim como indicado em alguns trabalhos já desenvolvidos. / Schizophrenia is a psychiatric disorder of significant importance for research in health care, however, despite being the target of numerous clinical and basic studies, there are still many doubts raised about its etiology, pathophysiology and treatment. In recent years, schizophrenia hypotheses that relate to changes in neurotransmitter systems have been very relevant. Currently, the glutamatergic hypothesis complements the dopaminergic, since blockade of NMDA glutamate receptors induces psychotic symptoms in healthy individuals and exacerbate them in patients with schizophrenia, suggesting that a hipofuncional state of these receptors may cause secondary changes in other neurotransmitter systems, leading to positive and negative symptoms and also to cognitive deficits of the disease. Cannabidiol (CBD) is a compound derived from Cannabis sativa that does not show neither the psychotomimetic effects nor side effect symptoms typically caused by the plant use, which are mostly attributed to delta-9-tetrahydrocannabinol (THC). Recently studies about the involvement of the endocannabinoid system in various physiological states and also in psychiatric disorders, suggest the therapeutic use of cannabinoids as a promising strategy for the prevention and control of some symptoms linked, for example, to anxiety, epilepsy and psychotic disorders. The antipsychotic profile of CBD has been confirmed in experimental 7 models and even in clinical trials, indicating that this compound is capable of preventing transient psychotic states caused both by THC and S (+)-ketamine (KET) in psychosis-induced models. The objective of this study was to enhance the existing information on the antipsychotic profile proposed for the CBD, however, three types of behavioral tasks were made for the analysis of three classes of psychotic-like symptoms in rodents, which are manifested through hyperlocomotion (positive symptoms), impairment in social interaction (negative symptoms) and a deficit in sensorimotor gating (cognitive deficits). The effects achieved with CBD are in accordance with the described in literature, a characteristic Ushaped curve and different pharmacological effects according to dose used. The analysis in the open field reveals that animals pretreated with CBD at a dose of 30 mg/kg shows a reduction in KET-induced hyperlocomotion, contrasting with the effects of CBD at a dose of 60 mg/kg, that enhances exploratory behavior after KET injection. In the PPI, the CBD at a dose of 30 mg/kg prevented the deficit caused by KET administration, showing effectiveness for the treatment of cognitive impairments that accompany psychosis; and enhances startle reflex when associated to KET. Therefore, with these results, it was demonstrated that CBD may be really effective for the treatment of certain symptoms of psychotic disorders, in accordance to some already developed studies.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-07-25T11:03:30Z No. of bitstreams: 2 Dissertação - Isis Gabrielli Barbieri de Oliveira - 2017.pdf: 1486050 bytes, checksum: fcc7f785120d547ad310a16b98732ea1 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-07-25T11:04:15Z (GMT) No. of bitstreams: 2 Dissertação - Isis Gabrielli Barbieri de Oliveira - 2017.pdf: 1486050 bytes, checksum: fcc7f785120d547ad310a16b98732ea1 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-07-25T11:04:15Z (GMT). No. of bitstreams: 2 Dissertação - Isis Gabrielli Barbieri de Oliveira - 2017.pdf: 1486050 bytes, checksum: fcc7f785120d547ad310a16b98732ea1 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-06-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The presence of circadian rhythms in organisms is a biological event, indispensable to the process of adaptation to the environment and fundamental for the survival of the species. The loss of the phase relationship between the biological rhythms and the behavior leads impairment of the body function. Thus, the aim of this study was to evaluate the effects of the forced locomotor activity desynchronization on the cardiovascular and metabolic parameters. Male Wistar rats, aged approximately 60 days, were distributed into two experimental groups: control group (CTR) submitted to the light/dark cycle (LD) of 24h-T24 (n=12) and desynchronized group (DSC) submitted to the LD cycle of 22h -T22 (n = 18) for eight weeks. Records of the locomotor activity were made daily to both groups. Food ingestion, water intake and body weight were monitored weekly. Following of this period the animals were allocated into two experimental protocols. In the first protocol the CTR and DSC animals were submitted to records of mean arterial pressure (MAP) and heart rate (HR), as well as pharmacological tests of baroreceptor reflex function and cardiac autonomic control, such as intrinsic pacemaker heart rate (IPHR); vagal and sympathetic effects and sympathetic-vagal index (SVI). In the second protocol, CTR and DSC animals were fasted for at least 12 hours, anesthetized and euthanized by decapitation to collect blood, liver and adrenal glands for posterior analysis of plasma glucose, triglycerides, total cholesterol, VLDL, HDL, LDL; the expression of proteins involved in the insulin signaling cascade (IR-β; IRS-2; PI3K; AKT), the gluconeogenic enzyme - PEPCK, SOD-1 and CAT; and morphometry. Although there was no significant difference in feed and water intake between groups, a higher weight gain of DSC animals was observed from week 7 onwards. In relation to the pattern of locomotor activity, DSC animals presented lower levels on total locomotor activity with a predominance of its activity during the light phase of the LD cycle. Although we did not observe significant alterations in the basal MAP and HR levels between the groups, the DSC animals showed reduction of the baroreflex sensitivity by the bradycardic index, as well as a higher cardiac sympathetic effect. No differences were observed between the groups for the other parameters of cardiac autonomic control. Regarding the biochemical parameters, we observed in the DSC animals, a reduction in HDL cholesterol associated with an increase in LDL cholesterol, which promoted a high index of Castelli I and II, compared to the CTR. There were no differences in plasma levels of glucose, triglycerides, total cholesterol and VLDL. DSC animals also showed an increase in weight and in the total area of the adrenal glands. In addition, we observed decreased IRβ, IRS-2, PI3-K and Akt proteins, as well as increased expression of the gluconeogenic enzyme PEPCK in DSC animals, suggesting hepatic insulin resistance. Finally, we observed a reduction in the expression of the SOD-1 and CAT enzymes in the DSC animals in relation to the CTR animals. Summarizing, our results suggest that a 22h symmetrical photoperiod (T-22) promotes lower baroreflex sensitivityand increased sympathetic effect on the heart. In addition, metabolic disorders such as hepatic insulin resistance and increased hepatic oxidative stress were observed in the desynchronized rats. / A presença de ritmos circadianos nos organismos é um evento biológico, indispensável ao processo de adaptação ao meio e fundamental para a sobrevivência das espécies. A perda de relação de fase entre os ritmos biológicos e o comportamento promovem prejuízo às funções orgânicas. Diante disso, o objetivo deste estudo foi avaliar os efeitos de uma dessincronização forçada da atividade locomotora nos parâmetros cardiovasculares e metabólicos. Ratos Wistar machos, com idade aproximada de 60 dias, foram distribuídos em dois grupos experimentais: grupo controle (CTR) submetido ao ciclo claro/escuro (CE) de 24h - T24 (n=12) e grupo dessincronizado (DSC) submetido ao ciclo claro/escuro (CE) de 22h - T22 (n=18) por oito semanas. Registros da atividade locomotora foram feitos diariamente para ambos os grupos. O consumo alimentar, ingestão de água e o peso corporal foram monitorados semanalmente. Ao final deste período os animais foram alocados em dois protocolos experimentais. No primeiro protocolo os animais CTR e DSC foram submetidos a registros da pressão arterial média (PAM) e frequência cardíaca (FC), bem como testes farmacológicos da função do reflexo barorreceptor e controle autonômico cardíaco, tais como frequência cardíaca intrínseca de marcapasso (FCIM); efeitos vagal e simpático e índice simpático-vagal (ISV). No segundo protocolo os animais CTR e DSC foram deixados em jejum de no mínimo 12 horas, anestesiados e eutanasiados por decapitação para coleta de sangue, fígado e glândulas adrenais para posterior análise dos níveis plasmáticos de glicose, triglicerídios, colesterol total, VLDL, HDL, LDL; da expressão de proteínas envolvidas na cascata de sinalização da insulina (IR-β; IRS-2; PI3K; AKT), enzima gliconeogênica – PEPCK, SOD-1 e CAT; e da morfometria. Embora não houve diferença significativa no consumo de ração e água entre os grupos, observou-se maior ganho de peso dos animais DSC a partir da 7ª semana. Em relação ao padrão da atividade locomotora os animais DSC apresentaram menor atividade locomotora total e um predomínio da mesma durante a fase clara do ciclo CE. Apesar de não observamos alterações significativas nos níveis de PAM e FC basais entre os grupos, os animas DSC apresentaram redução da sensibilidade barorreflexa pelo índice bradicárdico, assim como maior efeito simpático cardíaco. Não foram observadas diferenças entre os grupos para os demais parâmetros de controle autonômico cardíaco. Quanto aos parâmetros bioquímicos, observamos, nos animais DSC, redução do colesterol HDL associado a uma elevação do colesterol LDL, o que promoveu elevados índice de Castelli I e II comparados aos CTR. Não houve diferenças nos níveis plasmáticos de glicose, triglicerídios, colesterol total e VLDL. Os animais DSC também apresentaram aumento no peso e na área total das glândulas adrenais. Além disso, observamos diminuição das proteínas IRβ, IRS-2, PI3-K e Akt, bem como aumento da expressão da enzima gliconeogênica PEPCK nos animais DSC, sugerindo resistência hepática à insulina. Por fim observamos redução na expressão das enzimas SOD-1 e CAT nos animais DSC em relação aos animais CTR. Sumarizando, nossos resultados sugerem que um fotoperíodo simétrico de 22h (T-22) promove menor sensibilidade barorreflexa, maior efeito simpático sobre o coração. Além disso, foram observados distúrbios metabólicos, como resistência à insulina hepática e aumento do estresse oxidativo hepático, nos ratos dessincronizados.

Les rythmes biologiques aident les organismes vivants à programmer la plupart des processus comportementaux dans la fenêtre temporelle la plus appropriée. Les données de la littérature sur la rythmicité du chat domestique sont rares et conflictuelles. Pour approfondir nos connaissances sur le sujet, nous avons utilisé de récentes technologies de télémétrie pour enregistrer et caractériser les rythmes journaliers d'activité locomotrice et de prises alimentaire chez des chats en fonction des saisons et des conditions d’hébergement. Les rythmes des chats étaient modifiés par la photopériode et la présence humaine. Suivant une périodicité de 24 heures, ils ont affiché une bimodalité dans leurs rythmes quotidiens, avec des creux d'activité locomotrice et de consommation au milieu de la journée et de la nuit. Les deux périodes principales d'activité/alimentaires correspondaient à l'aube et au crépuscule à chaque saison, indépendamment de leur horaire, confirmant la nature intrinsèque crépusculaire de l'espèce. Le rythme alimentaire des chats était plus variable au cours du cycle que celui de leur activité locomotrice, rappelant ainsi le caractère opportuniste de ce prédateur. Les chats ont présenté une plasticité comportementale caractérisée par des rythmes plus faibles et un comportement d'exploration plus nocturne en milieu extérieur qu’en milieu intérieur, au sein duquel ils étaient plus enclins à la routine. Nos résultats ouvrent la voie au développement de solutions nutritionnelles et des recommandations d’hébergement adaptées aux rythmes du chat en respectant les besoins physiologiques de l’animal. / Biological rhythms are of importance for living organisms as they help to schedule most behavioural processes within the most suitable temporal window. Literature on daily rhythmicity is scarce and conflicting regarding domestic cats. To sharpen our knowledge on the subject, we used advanced telemetry technologies to record and characterise the daily rhythms of locomotor activity and feeding in cats according to the seasons and housing conditions. The cats were sensitive to photoperiod and to human presence. Along 24-hour periodicity, they displayed bimodality in their daily patterns, with mid-day and mid-night troughs of locomotor activity and food consumption. The two main activity/eating periods corresponded to dawn and dusk at each season, regardless of the twilight timings, confirming the crepuscular intrinsic nature of the species. The feeding rhythm of the cats was more variable daily than their locomotor activity one, recalling the opportunistic character of this predator. Cats displayed plasticity in their behaviour, such as weaker daily rhythms and more nocturnal exploratory behaviour outdoors, compared to indoors where they were more prone to routine. Our results open new avenues for developing nutritional and housing guidelines fitted to the rhythms of the cats according to their way of life.