Made available in DSpace on 2016-04-29T13:18:08Z (GMT). No. of bitstreams: 1 Luciana Roberta Donola Cardoso.pdf: 1323389 bytes, checksum: 152237ce34951aabd58677f712755d06 (MD5) Previous issue date: 2008-05-14 / The Chronic Mild Stress (CMS) is an experimental animal model of depression induced by the exposure of rats to a set of moderate and uncontrollable aversive stimuli in a long and uninterrupted period of time. The purpose of this study was to investigate the relationship between performance in variable interval schedule of behavior and exposure to the protocol of stress (daily consumption of food and water, changes in body weight, frequency of answers issued in each bar and the frequency of reinforcements obtained when submitted to the same scheme competitor). The study design was composed of three experimental conditions: test consumption and preferably liquid; sessions operating on schedule competitor VI 10 (water) VI 10 (sucrose) and protocol of stress (CMS). Six male rats were used. One subject was used to control weight, not involved in any of the three experimental conditions. Five subjects were submitted to the protocol of stress and tests of consumption and preference of liquids throughout the experiment. Two subjects were submitted to the working sessions (VI competitor VI) before and after CMS and two subjects were submitted to the working sessions before, during and after the CMS. The results were: 1) all subjects showed loss of body weight during the exposure to stressors. 2) The four subjects submitted to the working sessions showed recovery of body weight after the suspension of the protocol. 3) All subjects showed an increase in daily consumption of water and feed during the CMS, despite the loss of weight in this period. 4) Liquid consumption and the percentage of sucrose intake was higher during the CMS for the four subjects submitted to the working sessions, featuring a reduction in the last week of exposure to the protocol of stress. 5) All subjects expressed a greater number of responses in the bar corresponding to sucrose before exposure to CMS. Meanwhile, during and after CMS, a preference for water became outstanding. 6) The subjects received almost all of the planned reinforcements of both magnitudes (sucrose solution or pure water) in the three periods of assessment. We conclude that: 1) the loss of weight during the CMS seems to be related to the combination of aversive stimuli compound by the Protocol of stress and deprivation of water and food intermittent making up this protocol 2) the increase in the total consumption of liquids during the CMS appear to be related to the submission to the working sessions in variable interval before submission to the Protocol 3) the exposure of the subject to a scheme of variable interval, before CMS, slows the decline in the consumption of liquid and increases consumption of fluids during the CMS / O Chronic Mild Stress (CMS) é um modelo animal experimental de depressão induzida por meio da exposição de ratos a um conjunto de estímulos aversivos moderados e incontroláveis, apresentados por um longo e ininterrupto período de tempo. O objetivo deste estudo foi investigar a possível relação entre o desempenho em esquema de intervalo variável e a exposição ao protocolo de estresse, quanto ao consumo diário de ração e água e as subseqüentes alterações no peso corporal; no consumo e na preferência de líquidos; na freqüência de respostas emitidas em cada barra e na freqüência de reforços obtidos nas mesmas quando submetidos ao esquema concorrente. O delineamento foi composto por três condições experimentais: teste de consumo e de preferência de líquidos; sessões operantes em esquema concorrente VI 10 (água) VI 10 (sacarose) e protocolo de estresse (CMS). Foram utilizados seis ratos machos, sendo que um sujeito foi utilizado para controle de peso, não submetido a nenhuma das três condições experimentais. Cinco sujeitos foram submetidos ao protocolo de estresse e aos testes de consumo e preferência de líquidos durante todo o experimento. Dois sujeitos foram submetidos às sessões operantes (concorrente VI VI) antes e depois do CMS e dois sujeitos foram submetidos às sessões operantes, antes, durante e depois do CMS. Os resultados obtidos foram: 1) todos os sujeitos apresentaram perda de peso corporal durante a exposição aos estressores. 2) Os quatro sujeitos submetidos às sessões operantes apresentaram recuperação do peso corporal após a suspensão do protocolo; 3) todos os sujeitos apresentaram aumento no consumo diário de água e ração durante o CMS, apesar da perda de peso neste período; 4) consumo total de líquidos e a porcentagem de sacarose ingerida foi maior durante o CMS para os quatro sujeitos submetidos as sessões operantes, apresentando uma redução na última semana de exposição ao protocolo de estresse; 5) todos os sujeitos emitiram um maior número de respostas na barra correspondente a sacarose antes da exposição ao CMS. Entretanto, durante e depois do CMS a preferência por água se tornou sobressalente; 6) os sujeitos obtiveram a quase totalidade de reforços programados de ambas as magnitudes (solução de sacarose ou água pura ) nos três períodos de avaliação. Conclui-se que: 1) a perda de peso corporal durante o CMS parece estar relacionada à combinação dos estímulos aversivos compostos pelo protocolo de estresse e à privação de água e ração intermitente que compõem este protocolo 2) o aumento no consumo total de líquidos durante o CMS parecem estar relacionados à submissão às sessões operantes em intervalo variável antes da submissão ao protocolo 3) a exposição dos sujeitos a um esquema de intervalo variável, antes do CMS, não só teria um efeito de retardar a diminuição no consumo de líquidos, como aumentar o consumo de líquidos durante o CMS

Made available in DSpace on 2016-04-29T13:17:49Z (GMT). No. of bitstreams: 1 Najara Karine Salomao Pereira Almeida.pdf: 2355640 bytes, checksum: 39d43e135617768e1e42e6084f16eca9 (MD5) Previous issue date: 2013-05-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Chronic Mild Stress (SMS) is an anhedonia experimental animal model, induced by the chronic exposition of rats to a mild stressors protocol, and measured by the intake of sucrose, intracranial stimulation and/or site preference conditioning. Aside from anhedonia, this model is also recognized by the production of losses in the body weight, independently of specific feeding regimes and other characteristics analogous to the conditions that compose the depression diagnosis. The objective of the present study was to investigate if the exposition of the subjects to a water VT concurrent scheme water with sucrose 8% VT, of same value, before and after the stressors protocol, would produce disturbances: (1) in the body weight of the subjects; (2) in the diary consumption of food and water; (3) in the consumption and preference of liquids; (4) in the time during which the subjects remained close to the stimulus water and to the stimulus water with sucrose in the operant conditioning box, and (5) in the time in which the subjects have emitted responses in the site of the water fountain and of the water with sucrose 8% fountain. The design was composed by three experimental conditions: (1) exposition of the subjects VTP3, VTP4, VTP7, VTP8, P5, P6, P13 and P15 to the stressors protocol; (2) submission of the subjects VTP3, VTP4, VTP7 and VTP8 to the concurrent 20s VT sessions and (3) application of consumption and liquids´ preference tests in all of the experimental subjects, including the subject C10. The main disturbances noticed were: (a) decrease in the weight losses during the exposition to the protocol and decrease in weight variations during the role experiment; (b) diary water consumption similar to the ones of the subjects submitted to the FR and VI sessions; (c) increase in the diary food consumption, mainly during the exposition to the protocol; (d) constant consumption and preference by sucrose; (e) preference by sucrose in the 20s VT sessions after the exposition to the protocol, and (f) increase in the subjects´ general activity along the submission to the 20s VT sessions. The subjects exposed only to the protocol and to the liquid consumption tests didn´t present decrease in the sensibility to the reinforcer stimulus water with sucrose, what is commonly observed in other studies / Chronic Mild Stress (CMS) é um modelo animal experimental de anedonia, induzida através da exposição crônica de ratos a um protocolo de estressores pouco severos, e medida a partir de ingestão de sacarose, estimulação intracraniana e/ou condicionamento de preferência de lugar. Além de anedonia, este modelo também é reconhecido por produzir perda de peso corporal, independente de regime alimentar específico, e outras características análogas ao que compõe o diagnóstico de depressão. O objetivo do presente estudo foi investigar se a exposição de sujeitos a um esquema concorrente VT água VT água com sacarose a 8%, de mesmo valor, antes e após o protocolo de estressores, produzia alterações: (1) no peso corporal dos sujeitos; (2) no consumo diário de ração e água; (3) no consumo e preferência de líquidos; (4) no tempo em que os sujeitos permaneceram do lado do estímulo água ou do estímulo água com sacarose na caixa de condicionamento operante, e (5) no tempo em que os sujeitos emitiram respostas na região do bebedouro água ou do bebedouro água com sacarose a 8%. O delineamento foi composto por três condições experimentais: (1) exposição dos sujeitos VTP3, VTP4, VTP7, VTP8, P5, P6, P13 e P15 ao protocolo de estressores; (2) submissão dos sujeitos VTP3, VTP4, VTP7 e VTP8 as sessões concorrentes VT 20s e (3) aplicação dos testes de consumo e preferência de líquidos a todos os sujeitos da pesquisa, incluindo o sujeito C10. As principais alterações observadas foram: (a) menor diminuição de peso durante a exposição ao protocolo e menor variação de peso durante todo o experimento (b) consumo diário de água semelhante aos dos sujeitos submetidos às sessões de FR e VI; (c) aumento no consumo diário de ração, principalmente durante a exposição ao protocolo; (d) consumo de líquidos e preferência por sacarose constantes; (e) preferência por sacarose nas sessões VT 20s após a exposição dos sujeitos ao protocolo, e (f) aumento da atividade geral dos sujeitos ao longo da submissão às sessões VT 20s. Os sujeitos expostos somente ao protocolo e aos testes de consumo de líquido não apresentaram diminuição de sensibilidade ao estímulo reforçador água com sacarose comumente observado nos outros estudos

Made available in DSpace on 2016-04-29T13:17:49Z (GMT). No. of bitstreams: 1 Laura Muniz Rocha.pdf: 1241168 bytes, checksum: eaaf1dca965f9aa61ee39990e47879dd (MD5) Previous issue date: 2013-06-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Chronic Mild Stress (CMS) is an experimental animal model of induced anhedonia by exposing rats to a protocol of mild stressors for a long period of time. This model is an attempt to reproduce in controlled environment conditions analogous to the real environment, seen as important to produce behavioral changes. To identify other effects of exposure to CMS, this study aimed to verify whether the exposure to chronic mild stress produces changes in the establishment of a simple discrimination after the expouse to the protocol. Therefore, the subjects of this study had their weight and food and water intake measured daily, tests of consumption and preference of liquid were realized weekly; subjects were exposed to the protocol stressors over six weeks and, after this period was initiated the discriminative training. The experiment consisted of four experimental conditions: (1) one subject was exposed, like all other subjects, to tests of consumption and preference of liquids, (2) four subjects were exposed to the protocol, (3) four subjects were exposed to the protocol and to a discrimination procedure(4) four subjects were exposed only to the discrimination procedure and they weren t exposoused to the chronic mild stress. The results obtained in this study indicate that: (a) subjects exposed to the protocol showed a greater loss and variation of the body weight; (b) during the protocol the average of water consumption increased and average food consumption decreased for subjects exposed to the protocol. (c) tests of consumption and preference of liquids did not show a reduction in preference for the sucrose subtance but an increase in the total fluid intake for subjects exposed to stress. And, finally, (d) observed that exposure protocol stressors interfere with the acquisition of a simple discrimination. For subjects exposed to the protocol were required, on average, twice as many sessions to reach the criterion of two consecutive sessions with discriminative indices above 80%. and (e) that the subjects exposed to the protocol showed differences in tests of generalization when compared with subjects exposed only to discrimination. And, lastly (d) observed that exposure to the protocol interfered the acquisition of a simple discrimination. The subjects exposed to the protocol required, on average, twice as many sessions to reach the criterion of two consecutive sessions with discriminative indices above 80% and (e) the subjects exposed to the protocol showed differences in the generalization tests when compared with subjects exposed only to discrimination.Thereby, the exposure to a condition of chronic mild stress and affects the acquisition of a simple discrimination established after the protocol. This result may indicate that exposure to stress condition altered the reinforcing value of the stimulus for the subjects who were exposed to it, this change may have been responsible for the differences obtained in the discrimination of subjects exposed to this condition and subjects who were not exposed to the protocol / O Chronic Mils Stress (CMS) é um modelo animal experimental de anedonia induzida através da exposição de ratos a um protocolo de estressores crônicos e moderados por um longo período de tempo. Este modelo é uma tentativa de reproduzir, em ambiente controlado, condições análogas às do ambiente real, vistas como importantes para a produção de alterações comportamentais. Visando identificar outros efeitos da exposição ao CMS, o presente estudo teve como objetivo verificar se a exposição a eventos aversivos crônicos e moderados produz alterações no estabelecimento de uma discriminação simples posterior ao protocolo de estressores. Para tanto, os sujeitos do presente estudo tiveram o peso e o consumo de ração aferidos diariamente; foram expostos a testes semanais de consumo e preferência de líquidos; foram expostos ao protocolo de estressores ao longo de seis semanas e, após o encerramento deste, foi iniciado o treino discriminativo. O delineamento foi composto por quatro condições experimentais: (1) um sujeito foi exposto, como todos os outros sujeitos, aos testes de consumo e preferência de líquidos, (2) quatro sujeitos foram expostos ao protocolo de estressores, (3) quatro sujeitos foram expostos ao protocolo de estressores e a discriminação simples e (4) quatro sujeitos foram expostos a uma discriminação simples sem exposição aos estímulos crônicos e moderados. Os resultados obtidos no presente estudo indicam que: (a)os sujeitos expostos ao protocolo de estressores apresentaram uma maior perda e variação no peso corporal; (b) durante o protocolo o consumo médio de água aumentou e o consumo médio de ração diminuiu para os sujeitos expostos ao protocolo. (c) nos testes de consumo e preferência de líquidos não foi observado uma redução na preferência por sacarose e sim um aumento no consumo total de líquidos para os sujeitos expostos a condição de estresse. E, por fim, (d) observou-se que a exposição ao protocolo de estressores interferiu na aquisição de uma discriminação simples. Para os sujeitos expostos ao protocolo foram necessárias, em média, o dobro de sessões para atingir o critério de duas sessões consecutivas com índices discriminativos superiores a 80% e (e) que os sujeitos expostos ao protocolo apresentaram diferenças nos testes de generalização se comparados com os sujeitos expostos somente à discriminação. Assim, é possível concluir que a exposição a uma condição de estresse crônica e moderada afeta a aquisição de uma discriminação simples posteriormente estabelecida. Esse resultado pode indicar que a exposição à condição de estresse alterou o valor reforçador do estímulo para os sujeitos que foram expostos a ele, essa alteração pode ter sido responsável pelas diferenças obtidas na discriminação dos sujeitos expostos a essa condição e dos sujeitos que não foram expostos aos estressores

Made available in DSpace on 2016-04-29T13:17:55Z (GMT). No. of bitstreams: 1 Paulo Eduardo da Silva.pdf: 1304608 bytes, checksum: 120f5cf5c36c91fabfb9829aab88df3f (MD5) Previous issue date: 2015-07-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Chronic Mild Stress (CMS) has been described in the literature as an experimental model of anhedonia, central symptom of depression in humans. The anhedonia has been studied in this model looking for a decrease of water with sucrose consumption in rats. This result is usually observed after the animal had been subjected to a set of stressful stimuli in a moderated and chronical way, for six weeks in average. The present study aimed to investigate the effects of the Stressors Protocol in rats subjected to a continuous water deprivation regimen. Eleven male rats of Wistar lineage were studie,. All the rats were subjected to a water deprivation schedule until reaching 85% of their ad lib weights, and they were maintained at these weights for the whole study. Thirteen water and water with sucrose consumption tests were used for all the subjects, while S7 was exposed only to the liquids consumption tests. S3 subject was submitted only to the Stressors Protocol. S5 was exposed to the same conditions of S3, except that the Stressors Protocol involved only the grouping stressor. For the other eight subjects, first they had the bar press response to the two bars modeled, using water as reinforcement. Then these eight animals were subjected to a Conc VI 5 sec VI 5 sec reinforcement, each bar being associated to water or water with sucrose reinforcements (one for each bar). After four weeks in this reinforcement schedule these animals were subjected to the Stressors Protocol for six consecutive and uninterrupted weeks in their living cages. During the protocol, four subjects (S2, S6, S8 and S10) also had their bar press responses reinforced in a Conc VI 5 sec VI 5 sec schedule (group before, during and after). The other four rats (S1, S4, S9 and S11- group before and after) were not submitted to operant sessions as long as the Stressors Protocol was available. At the end of the phase when the Stressors Protocol was available, these eight subjects were again subjected to the base line condition. The main results were: (a) a weight stability for the animals subjected to the protocol, (b) a high alternation of water and water with sucrose consumption in the tests for the only subject submitted to the tests and to the protocol, not demonstrating anhedonia, (c) a reduction in the animal s food consumption and an increase of water consumption in the living cage during the protocol for seven subjects, (d) the stressors protocol was not followed by a modification of the distribution of water and water with sucrose reinforced responses by Conc VI 5sVI5s, neither during the protocol, nor after its cessation, and (e) it seems that the reinforcement value of the liquids alternated for some subjects over major of the sessions. The role of continuous water deprivation and the measures used as anhedonia indicators are discussed / O Chronic Mild Stress (CMS) tem sido descrito na literatura como um modelo experimental de anedonia, sintoma central na depressão em humanos. A anedonia tem sido estudada dentro desse modelo a partir do decréscimo no consumo de água com sacarose em ratos. Este resultado é geralmente observado após o animal ser submetido a um conjunto de estímulos estressores de forma moderada e crônica, durante seis semanas em média, O presente estudo teve como objetivo investigar os efeitos do Protocolo de Estressores em ratos submetidos a um regime contínuo de privação de água. Foram empregados 11 ratos machos, da linhagem Wistar. Todos os sujeitos foram submetidos a um esquema de privação de água até atingir 85% dos seus pesos ad lib. e foram mantidos nesses pesos durante todo o estudo. Foram empregados 13 testes de consumo de água e de água com sacarose, sendo que o Sujeito S7 só passou pelos testes de consumo dos líquidos. O Sujeito S3 foi submetido ao Protocolo de Estressores. O sujeito S5 passou pelas mesmas condições que o S3, exceto que o Protocolo de Estressores envolveu apenas o estressor agrupamento. Para os outros 8 sujeitos, primeiramente foram modeladas as respostas de pressão às duas barras, usando água como reforçador. Depois, esses 8 animais foram submetidos a um esquema Conc VI 5 seg VI 5 seg associado aos reforços água e água com sacarose (um para cada barra). Após quatro semanas nesse esquema de reforçamento esses animais foram submetidos ao Protocolo de Estressores por seis semanas consecutivas e ininterruptas nas suas gaiolas-viveiro. Durante o Protocolo, 4 sujeitos (S2, S6, S8, S10) também tiveram suas respostas de pressão à barra reforçadas num esquema Conc VI 5 seg VI 5 seg (grupo antes, durante e depois) e os outros 4 (S1, S4, S9, S11) não (grupo antes e depois). Ao término do Protocolo de estressores, esses 8 sujeitos foram submetidos novamente à condição de linha de base. Os principais resultados encontrados foram: (a) estabilidade nos pesos dos animais submetidos ao protocolo, (b) maior oscilação em relação ao consumo de água e de água com sacarose para o sujeito submetido apenas aos testes e ao protocolo, não demonstrando anedonia, (c) redução no consumo de ração e aumento no consumo de água na gaiola-viveiro durante o protocolo (d) o protocolo de estressores não foi acompanhada por uma alteração na distribuição de respostas reforçadas com água e água com sacarose, nem durante e nem após a suspensão do mesmo, e (e) o valor reforçador dos líquidos parece ter se alternado para alguns sujeitos ao longo da maioria das sessões. Discute-se o papel da privação contínua de água e as medidas utilizadas como indicativas a de anedonia

<div>Ketogenic diets (KDs) are high-fat low-carbohydrate diets that can exert positive effects on physical and neurological health. The more established therapeutic effects of KD are for treating epilepsy and diabetes. However, KD protective effects may apply to other inflammation related disorders associated with Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation, such as mood disorders. Chronic stress has been shown to elevate cytokine levels, disrupt neuroendocrine homeostasis, and cause anxiety and depressive-like behavior in animal models. In vitro experiments have shown that ketone bodies, a metabolite produced while on KD, can prevent the production of cytokines elevated in response to chronic stress and other pre-clinical experiments have suggested that ketone bodies can prevent anxiety-like behavior. Although this suggests that KDs have anti-inflammatory and mood stabilizing potential, these effects have yet to be explored. In this experiment, we assessed the behavioral and neuroendocrine effects of KD using male and female Long-Evans rats. Animals underwent three weeks of Chronic Mild Stress (CMS) while on KD or control Chow (CH). Body weight and food intake data were recorded daily, and depressive-like behaviors were assayed after the three weeks. Plasma Beta-Hydroxybutyrate (HB), Corticosterone (CORT) and Interleukin-1 beta (IL-1) were measured after behavior testing, along with hypothalamic Corticotropin-Releasing Hormone (CRH) and Neuropeptide Y (NPY) mRNA expression. CMS induced weight loss and reduced food intake in the control-diet groups, however the KD-fed male and female rats were resistant to CMS-induced weight loss and reduced food take. Female rats fed KD were protected from CMS-induced reductions in plasma CORT and hypothalamic NPY expression. Collectively, these data suggest anti-depressant potential of KDs against chronic stress, particularly in females. </div>

With chronic post surgical pain affecting up to one third of patients undergoing surgeries and the price of treatment being astoundingly high there has been a transition in research to investigate and identify risk factors. Through identification of risk factors new preventative measures can be taken to ensure better surgical outcomes. The role that psychosocial factors can play in the development of chronic post surgical pain has long been recognized yet its mechanisms are still unknown. We aim to investigate how environment can play a direct role in pain perception and sensitivity. We used a Chronic Mild Stress (CMS) paradigm to induce depression in 10 adult male mice, we used 10 control mice who were left in standard opti cages, and 10 enriched mice who were placed in large enrichment cages. CMS mice were exposed to a series of stressors and all mice underwent spared nerve injury surgery. During spared nerve injury the common peroneal and tibial branches of the sciatic nerve were severed while the sural branch was left intact. Overall well-being and pain threshold of mice were tested via Von Frey, Hot Plate, Heat Place Preference, Dynamic Weight Bearing, Hole Board, and Social Interaction. It was found that CMS mice experienced thermal hyperalgesia yet normal thermal threshold sensation. CMS mice also spent less time interacting with novel mice in social interaction, and less amount of time exploring the center of the hole board arena than control or enriched mice. While Von Frey results did not change over the course of the experiment, dynamic weight bearing results indicated spared nerve injury surgery was successful and produced chronic pain. Results indicate that environment plays a role in thermal pain perception and CMS affected overall well being of mice as CMS mice exhibited more timid and anxious behavior.

Major depressive disorder (MDD) affects 300 million people worldwide and is a major contributor to the global burden of disease. The aetiology of depression, emerging through a gene x environment interaction, is still incompletely understood which prevents tailoring of treatment approaches. In addition to MDD core symptoms, such as anhedonia (a diminished anticipation or experience of pleasure), depressed patients suffer from a plethora of manifestations including cognitive impairments, which occur primarily in the domains of executive function, attention and memory. Patients remitted from affective symptoms of MDD often continue to display cognitive impairments. These cognitive deficits are the longest present residual symptom, predict treatment response and increase risk of relapse. Consequently, cognitive impairments need to be targeted more effectively by antidepressants for complete remission from MDD. Clinically relevant animal models are essential for developing, tailoring and testing such novel, pro-cognitive antidepressants. This PhD project aimed to establish a preclinical screening platform for the testing of pro-cognitive antidepressants, to improve understanding of MDD risk factors and consequent symptom development, and finally, to focus on clinical relevance of the applied techniques. The chronic mild stress (CMS) rodent model of depression was used, known for displaying the core symptom anhedonia, but also for a high construct, face and predictive validity. The environmental MDD risk factor 'stress' induces an anhedonic-like phenotype in a subgroup of exposed rats, whereas another subgroup of rats is resilient, as determined by the sucrose consumption test. The cognitive performance of different rat strains, including CMS anhedonic-like and resilient rats, was assessed employing the touchscreen operant platform, which was developed based on the Cambridge neuropsychological test automated battery (CANTAB) for assessing cognition in humans. Furthermore, a group of anhedonic-like rats was treated with the antidepressant vortioxetine, which acts as both a pro-cognitive and antidepressant treatment. Our results showed that stress exposure induced anhedonia in albino and pigmented rat strains, although stress did not affect cognitive performance of pigmented rats in a simple pairwise discrimination touchscreen task. Applying a more complex pairedassociates learning touchscreen task revealed impaired cognitive performance in the CMS anhedonic-like but not in the resilient phenotype. Furthermore, vortioxetine treatment reversed anhedonia in the CMS model and altered executive functions in treated rats. The expression of genes involved in the stress response, affective disorders and neuronal plasticity was altered in the prefrontal cortex and hippocampus owned to treatment and hedonic state. Thus, we have demonstrated that the CMS model exhibits both stress-induced cognitive alterations and depression-associated cognitive impairments in touchscreen tasks. Furthermore, touchscreen testing was sufficiently sensitive to detect alterations in cognitive performance due to pharmacological intervention. Overall, we established a potential platform for pro-cognitive antidepressant drug screening. Furthermore, brain derived neurotrophic factor (BDNF), involved in learning and memory, was examined in the context of depression. BDNF is reduced in MDD patients as well as in preclinical models in response to stress. Although this suggests that BDNF contributes to the aetiology of depression, studies including mice heterozygous for BDNF (BDNF+/-) have generated conflicting results. BDNF+/- rats may provide a more suitable model as (1) rats have a greater behavioural repertoire than mice, (2) classical behaviour tests are designed for rats, and (3) rats, like humans, produce peripheral BDNF. We found anhedonia and mild signs of anxiety in BDNF+/- rats, accompanied by prefrontal and hippocampal changes in expression of genes relevant in psychiatric disorders and underpinning learning. Thus, behavioural and molecular findings in BDNF+/- rats complement existing literature and suggest that rats are a more suitable model in BDNF research than mice. Overall, the project uncovered environmental and genetic manifestations of risk factors in translational models and established a novel tool for translational pro-cognitive antidepressant drug screening.

Women are twice as likely to suffer from depression as men, yet stress and depression research has relied primarily on the responses of males. Early life stress is hypothesized to influence the development of vulnerability to depression while adult stress exposure can act as a trigger in those predisposed. This relationship is mediated by other environmental factors. Maternal care and the social environment appear to be particularly important for mammals. The purpose of this thesis was twofold: to develop an animal model of depression for use in female rats based on the chronic mild stress (CMS) model previously validated for use in male rodents, and to apply this model in female offspring of mothers exposed to physical restraint in the second half of gestation representing an early life insult. Results indicate that a modified CMS model was able to alter hedonic and physiological responses not present in the original model. Housing condition interacted with CMS in that effects were evident only in singly housed rats. While gestational stress (GS) altered maternal weight and behavioural profiles related to offspring care and anxiety, little to no behavioural effects were noted in juvenile or adult offspring. Applying the modified CMS model to adult female offspring resulted in an anhedonic-like response that recovered rapidly prior to the third week of CMS. Weight in GS female rats was attenuated throughout life beginning post weaning. When taken together, these results demonstrate that stress-based models, previously established in males, must be altered to accommodate the hormonally intact female rat in two ways: first, to eliminate extraneous variables that may interfere with the estrous cycle and mask possible stress effects, and secondly, to consider the appropriateness of individual stressors to induce a stress response in females. While a general lack of effect was noted in response to CMS, this was interpreted as a strong influence of housing and supportive early life experiences in protecting the female rat from the establishment of stress effects related to depression and anxiety. The housing practices employed here may be considered a model of stress-resilience and represents an encouraging avenue of future research.

Women are twice as likely to suffer from depression as men, yet stress and depression research has relied primarily on the responses of males. Early life stress is hypothesized to influence the development of vulnerability to depression while adult stress exposure can act as a trigger in those predisposed. This relationship is mediated by other environmental factors. Maternal care and the social environment appear to be particularly important for mammals. The purpose of this thesis was twofold: to develop an animal model of depression for use in female rats based on the chronic mild stress (CMS) model previously validated for use in male rodents, and to apply this model in female offspring of mothers exposed to physical restraint in the second half of gestation representing an early life insult. Results indicate that a modified CMS model was able to alter hedonic and physiological responses not present in the original model. Housing condition interacted with CMS in that effects were evident only in singly housed rats. While gestational stress (GS) altered maternal weight and behavioural profiles related to offspring care and anxiety, little to no behavioural effects were noted in juvenile or adult offspring. Applying the modified CMS model to adult female offspring resulted in an anhedonic-like response that recovered rapidly prior to the third week of CMS. Weight in GS female rats was attenuated throughout life beginning post weaning. When taken together, these results demonstrate that stress-based models, previously established in males, must be altered to accommodate the hormonally intact female rat in two ways: first, to eliminate extraneous variables that may interfere with the estrous cycle and mask possible stress effects, and secondly, to consider the appropriateness of individual stressors to induce a stress response in females. While a general lack of effect was noted in response to CMS, this was interpreted as a strong influence of housing and supportive early life experiences in protecting the female rat from the establishment of stress effects related to depression and anxiety. The housing practices employed here may be considered a model of stress-resilience and represents an encouraging avenue of future research.

Women are twice as likely to suffer from depression as men, yet stress and depression research has relied primarily on the responses of males. Early life stress is hypothesized to influence the development of vulnerability to depression while adult stress exposure can act as a trigger in those predisposed. This relationship is mediated by other environmental factors. Maternal care and the social environment appear to be particularly important for mammals. The purpose of this thesis was twofold: to develop an animal model of depression for use in female rats based on the chronic mild stress (CMS) model previously validated for use in male rodents, and to apply this model in female offspring of mothers exposed to physical restraint in the second half of gestation representing an early life insult. Results indicate that a modified CMS model was able to alter hedonic and physiological responses not present in the original model. Housing condition interacted with CMS in that effects were evident only in singly housed rats. While gestational stress (GS) altered maternal weight and behavioural profiles related to offspring care and anxiety, little to no behavioural effects were noted in juvenile or adult offspring. Applying the modified CMS model to adult female offspring resulted in an anhedonic-like response that recovered rapidly prior to the third week of CMS. Weight in GS female rats was attenuated throughout life beginning post weaning. When taken together, these results demonstrate that stress-based models, previously established in males, must be altered to accommodate the hormonally intact female rat in two ways: first, to eliminate extraneous variables that may interfere with the estrous cycle and mask possible stress effects, and secondly, to consider the appropriateness of individual stressors to induce a stress response in females. While a general lack of effect was noted in response to CMS, this was interpreted as a strong influence of housing and supportive early life experiences in protecting the female rat from the establishment of stress effects related to depression and anxiety. The housing practices employed here may be considered a model of stress-resilience and represents an encouraging avenue of future research.