Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Circadian rhythms are ubiquitous among organisms, influencing a wide array of physiological processes and behaviors including aggression. While many neurophysiological mechanisms are involved in the regulation of aggressive behaviors, relatively few studies have investigated the underlying components involved in the interplay between circadian rhythms and aggression. Spiders are an ideal model system for studying circadian regulation of aggression as they are ecologically both predators and prey. Recent studies have revealed a nocturnal orb- weaving spider Larinioides cornutus exhibits a diel and circadian rhythm in anti-predator behavior (i.e. boldness) that can be manipulated by administration of octopamine (OA) and serotonin (5- HT). Dosing of OA increases boldness of an individual while 5-HT decreases boldness levels. Thus, it appears the serotonergic and octopaminergic system are playing a key role in the daily fluctuations of boldness. This study took a holistic approach to investigate OA and 5-HT levels of head tissue and hemolymph (i.e. blood) as well as the genes involved in synthesis, signaling, and degradation of these monoamines throughout the day (0100, 0700, 1300, and 1900 hours) using HPLC-ED and RNA-sequencing. Although endogenous and circulating levels of OA did not significantly fluctuate, putative transcripts involved in synthesis and signaling did increase in relative expression levels at dusk when L. cornutus begins to actively forage for prey. Endogenous and circulating levels of 5-HT also did not significantly change at the four different time points, but clear patterns of upregulation of 5-HT synthesis enzymes as well as some receptor transcripts were upregulated during the day when L. cornutus would be mostly inactive in its retreat. Lastly, monoamine oxidase, a major catabolic enzyme of monoamines in vertebrates and some invertebrates, was identified in L. cornutus and exhibited substrate specificity for OA compared to 5-HT. Together with the higher enzymatic activity at mid-day compared to dusk, MAO appears to be playing a significant role in regulating the OA and 5-HT signaling in L. cornutus. In conclusion, these results allow a unique preliminary perspective on how OA and 5-HT are influencing the diel shifts in aggression-related behaviors in an ecologically dynamic arthropod.

Ketamine is a non-competitive NMDA antagonist that has been shown to have antidepressant properties both clinically as well as in preclinical studies when administered at a subanesthetic dose. In vivo electrophysiological recordings were carried in male Sprague Dawley rats 30 minutes following ketamine administration (10 mg/kg) to first assess its effects on monoaminergic firing. Whilst no change in the firing activity of serotonin (5-HT) neurons was observed in the dorsal raphe nucleus (DRN), an increase in the firing activity was observed for dopamine (DA) and noradrenergic (NE) neurons in the ventral tegmental area (VTA) and locus coeruleus (LC), respectively. The effect of ketamine on these electrophysiological parameters was prevented by pre-administration of the AMPA receptor antagonist NBQX 10 minutes prior to ketamine administration. In a second series of experiments, an increase in AMPA-evoked response was observed within 30 minutes in the CA3 layer of the hippocampus (HPC) following acute ketamine administration. These findings suggest that acute ketamine administration produces a prompt enhancement of AMPA transmission in the forebrain and also results in increased catecholaminergic activity. These effects may play a crucial role in the rapid antidepressant effects of ketamine observed shortly following its infusion in the clinic.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A depressÃo à uma doenÃa recorrente e incapacitante cujo tratamento està relacionado com modulaÃÃes nos sistemas monoaminÃrgicos em diversas Ãreas cerebrais. A riparina III (ripIII), isolada do fruto verde de Aniba riparia, apresentou, em estudos prÃvios, efeito antidepressivo. Dessa forma, objetivando investigar o potencial antidepressivo da ripIII, foram realizados testes comportamentais como o nado forÃado (TNF), suspensÃo da cauda (TSC), hipotermia induzida por apomorfina e campo aberto. Para avaliar o envolvimento das monoaminas, os animais foram prÃ-tratados com antagonistas especÃficos para receptores 5-HT1A, 5-HT2A/2C e 5-HT3 de serotonina (5-HT), D1 e D2 de dopamina (DA) e a1 e a2 de noradrenalina (NA) no TNF. AlÃm disso, os animais prÃ-tratados com ripIII e submetidos ou nÃo ao TNF tiveram as Ãreas cerebrais hipocampo, corpo estriado e cÃrtex prÃ-frontal retiradas para detecÃÃo dos nÃveis de monoaminas ou para realizaÃÃo dos experimentos de estresse oxidativo, investigando a atividade enzimÃtica da catalase e superÃxido dismutase, quantificando os nÃveis de glutationa reduzida (GSH) e nitrito/nitrato, alÃm do grau de lipoperoxidaÃÃo. A ripIII foi administrada agudamente, por via oral, na dose de 50 mg/kg, em todos os testes. Os resultados mostraram que a ripIII apresentou efeito antidepressivo nos modelos TNF e TSC sugerindo ser especÃfico, uma vez que os animais nÃo apresentaram alteraÃÃes na atividade locomotora no campo aberto. AlÃm disso, no TNF, os antagonistas sulpirida (D2), prazosina (a1), ioimbina (a2), NAN-190 (5-HT1A) e ondansentron (5-HT3) reverteram o tempo de imobilidade da ripIII sugerindo a participaÃÃo desses receptores para o efeito da substÃncia, enquanto nÃo houve alteraÃÃo deste efeito na presenÃa dos antagonistas SCH23390 (D1) e ritanserina (5- HT2A/2C) mostrando o nÃo envolvimento desses receptores no efeito da droga. A ripIII nÃo foi capaz de reverter a hipotermia induzida por apomorfina, que na dose utilizada, induz hipotermia por modular receptores b-adrenÃrgicos, sugerindo que o efeito da ripIII nÃo està relacionado com esses receptores. A ripIII apÃs o TNF, em corpo estriado e cÃrtex prÃfrontal, aumentou os nÃveis de DA, 5-HT e NA, diminuiu os metabÃlitos DOPAC, HVA, 5- HIAA e as taxas metabÃlicas e, no hipocampo, aumentou 5-HT e NA alÃm do metabÃlito 5- HIAA, mas manteve as taxas metabÃlicas. A administraÃÃode ripIII, antes do TNF, reverteu o aumento nos nÃveis de peroxidaÃÃo lipÃdica e nitrito-nitrato, reduziu a atividade da catalase mas aumentou os nÃveis de GSH em hipocampo, corpo estriado e cÃrtex prÃfrontal. Esses parÃmetros nÃo foram alterados nos animais nÃo submetidos ao estresse. Em conclusÃo, o estudo sugere uma aÃÃo moduladora, exercida por ripIII, sobre o funcionamento dos sistemas noradrenÃrgico, dopaminÃrgico e serotonÃrgico, em nÃvel central, como mecanismo para o efeito antidepressivo no TNF, bem como a participaÃÃo de propriedades antioxidantes diretas ou indiretas dessa droga, atravÃs da capacidade de modificar a resposta ao estresse oxidativo neuronal. / Depression is a disabling and recurrent disease whose treatment is related to modulations in monoaminergic systems in several brain areas. Riparin III (ripIII), isolated from unripe fruit of Aniba riparia, has shown previously antidepressant-like effects. Thus, in order to investigate the antidepressant effect of ripIII, behavioral experiments were performed, as the forced swim (FST), tail suspension (TST), apomorphine-induced hypothermia and open field tests. To assess the involvement of monoaminergic system, animals were pretreated with specific antagonists to 5-HT1A-, 5-HT2A/2C-, and 5-HT3-serotonin (5-HT) receptors, to D1- and D2-dopamine (DA) receptors and to 1- and 2-noradrenaline (NA) receptors in FST. Further, animals pretreated with ripIII and submitted or not to the FST had their brain areas such as hippocampus, striatum and prefrontal cortex removed for detection of monoamine levels or to carry out the experiments of oxidative stress, in which, it was investigated enzymatic activities of catalase and superoxide dismutase, measured the levels of reduced glutathione (GSH) and nitrite/nitrate, and lipid peroxidation degree. RipIII was acutely administered orally at a dose of 50 mg/kg in all tests. The results showed that ripIII presented antidepressant effect on the FST and TST suggesting that this effect is specific, since the animals showed no changes in locomotor activity in open field test. In the evaluation of monoaminergic systems, the results showed that the antagonists sulpiride (D2), prazosin (1), yohimbine (2), NAN-190 (5-HT1A) and ondansentron (5-HT3) reversed the immobility time of ripIII on the FST suggesting the involvement of these receptors, while no change of this effect in the presence of the antagonists SCH23390 (D1) and ritanserin (5-HT2A/2C) was observed, suggesting non-participation of these receptors in the drug effect. RipIII was unable to reverse the hypothermia induced by apomorphine that at the dose used, modulates -adrenergic receptors inducing hypothermia, suggesting that the effect of ripIII is not related to these receptors. RipIII, after FST, in the striatum and prefrontal cortex, increased levels of DA, 5-HT and NA, decreased DOPAC, HVA, 5-HIAA metabolites and decreased metabolic rates, and in the hippocampus, increased 5-HT and NA and 5-HIAA metabolite, but maintained metabolic rates. The prior administration of ripIII before the forced swimming, reversed the increased levels of lipid peroxidation and nitrite-nitrate, reduced the activity of catalase but increased levels of GSH in hippocampus, striatum and prefrontal cortex. These parameters were not altered in animals not exposed to stress. In conclusion, the study suggests a modulating action exerted by ripIII on the functioning of the noradrenergic, dopaminergic and serotonergic levels in the brain, as a mechanism for the antidepressant effect in the FST, as well as the participation of direct or indirect antioxidant properties of this drug through the ability to modify the neuronal response to oxidative stress

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / A depressÃo à uma doenÃa recorrente e incapacitante cujo tratamento clÃnico està relacionado com modulaÃÃes nos sistemas monoaminÃrgicos em diversas Ãreas cerebrais. A riparina II (ripII), alcamida isolada do fruto verde de Aniba riparia, apresentou previamente efeito antidepressivo em modelos comportamentais. Dessa forma, objetivando investigar o potencial antidepressivo da ripII, foram realizados experimentos comportamentais como o teste do nado forÃado, suspensÃo da cauda e campo aberto. Para avaliar o envolvimento do sistema monoaminÃrgico, os animais foram prÃ-tratados com antagonistas especÃficos para receptores 5-HT1A, 5-HT2A/2C e 5-HT3 de serotonina (5-HT), D1 e D2 de dopamina (DA) e a1 e a2 de noradrenalina (NA) no teste do nado forÃado. AlÃm disso, os animais previamente tratados com ripII e submetidos ao teste do nado forÃado tiveram as Ãreas cerebrais hipocampo, corpo estriado e cÃrtex prÃ-frontal retiradas para detecÃÃo dos nÃveis de monoaminas em HPLC eletroquÃmico ou para realizaÃÃo dos experimentos de estresse oxidativo, para o qual foram investigadas a atividade enzimÃtica da superÃxido dismutase, quantificaÃÃo dos nÃveis de glutationa reduzida (GSH) e nitrito/nitrato, alÃm do grau de lipoperoxidaÃÃo. A ripII foi administrada agudamente, por via oral, na dose de 50 mg/kg, em todos os testes realizados. Os resultados mostraram que a ripII apresentou efeito antidepressivo nos modelos de nado forÃado e suspensÃo da cauda sugerindo que este efeito seja especÃfico, uma vez que os animais nÃo apresentaram alteraÃÃes na atividade locomotora no teste do campo aberto. Na avaliaÃÃo dos sistemas monoaminÃrgicos, os resultados mostraram que os antagonistas SCH23390 (D1), sulpirida (D2), prazosina (a1), NAN-190 (5-HT1A) e ondansentron (5-HT3) reverteram o tempo de imobilidade da ripII no nado forÃado sugerindo a participaÃÃo desses receptores para o efeito antidepressivo da substÃncia, enquanto nÃo houve alteraÃÃo deste efeito na presenÃa dos antagonistas ioimbina (a2) e ritanserina (5-HT2A/2C) sugerindo a nÃo participaÃÃo desses receptores no efeito da droga. A administraÃÃo prÃvia de ripII, antes do nado forÃado, reverteu o aumento nos nÃveis de peroxidaÃÃo lipÃdica, mas aumentou os nÃveis de GSH em hipocampo, corpo estriado e cÃrtex prÃ-frontal. Em conclusÃo, o estudo sugere uma aÃÃo moduladora, exercida por ripII, sobre o funcionamento dos sistemas noradrenÃrgico, dopaminÃrgico e serotonÃrgico, em nÃvel central, como mecanismo para o efeito antidepressivo no teste do nado forÃado, bem como a participaÃÃo de propriedades antioxidantes diretas ou indiretas dessa droga, atravÃs da capacidade de modificar a resposta ao estresse oxidativo neuronal. / Depression is a disabling and recurrent disease whose clinical treatment is related to modulations in monoaminergic systems in various brain areas. Riparina II (ripII), alkamide isolated from unripe fruit of Aniba riparia, has shown previously antidepressant-like effects in animal behavioral models. Thus, in order to investigate the potential antidepressant ripII, behavioral experiments were performed as the forced swim, tail suspension and open field tests. To assess the involvement of monoaminergic system, animals were pretreated with specific antagonists to 5-HT1A-, 5-HT2A/2C-, and 5-HT3-serotonin (5-HT) receptors, to D1- and D2-dopamine (DA) receptors and to 1- and 2-noradrenaline (NA) receptors in the forced swimming test. Furthermore, animals pretreated with ripII and submitted to the forced swim test had their brain areas such as hippocampus, striatum and prefrontal cortex removed for detection of monoamine levels in HPLC electrochemical or to carry out the experiments of oxidative stress. In the oxidative stress assays we investigated enzymatic activities of superoxide dismutase, measured the levels of reduced glutathione (GSH) and nitrite/nitrate, and lipid peroxidation degree. RipII was acutely administered orally at a dose of 50 mg/kg in all tests. The results showed that ripII presented antidepressant effect on the forced swim and tail suspension tests suggesting that this effect is specific, since the animals showed no changes in locomotor activity in open field test. In the evaluation of monoaminergic systems, the results showed that the antagonists SCH23390 (D1), sulpiride (D2), prazosin (1), NAN-190 (5-HT1A) and ondansentron (5-HT3) reversed the immobility time of ripII on the forced swim test suggesting the involvement of these receptors for the antidepressant effect of ripII, while no change of this effect in the presence of the antagonists yohimbine (2) and ritanserin (5-HT2A/2C) was observed, suggesting non-participation of these receptors on the drug effect. The prior administration of ripII before the forced swimming, reversed the increased levels of lipid peroxidation and increased levels of GSH in hippocampus, striatum and prefrontal cortex. In conclusion, the study suggests a modulating action exerted by ripII on the functioning of the noradrenergic, dopaminergic and serotonergic levels in the brain, as a mechanism for the antidepressant effect in the forced swimming test, as well as the participation of direct or indirect antioxidant properties of this drug through the ability to modify the neuronal response to oxidative stress.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A cocaÃna à uma droga consumida mundialmente e considerada hoje como um problema de saÃde pÃblica. Uma das principais dificuldades enfrentadas no combate ao vÃcio da cocaÃna, na maioria dos casos, està relacionada aos sintomas de abstinÃncia da droga, como ansiedade, depressÃo, irritabilidade, fadiga e insÃnia, fazendo com que o indivÃduo volte a procurÃ-la. Para avaliar as alteraÃÃes comportamentais (ansiedade e depressÃo) e neuroquÃmicas, os ratos foram submetidos Ãs retiradas de 24 h, 7 d e 21 d apÃs o tratamento subcrÃnico por 7 dias com cocaÃna (20mg/kg), sendo realizados os modelos experimentais de Labirinto de Cruz Elevado (LCE), Campo Aberto (CA) e Nado ForÃado (NF). AlÃm disso, na abstinÃncia de 24h foram testados o propranolol (10mg/kg, i.p.), o ondansetrom (4mg/kg, i.p) e a buspirona (5 mg/kg, i.p.), no LCE e CA, bem como na abstinÃncia de 21 d foram testados a bupropiona (30mg/kg, i.p.) e paroxetina (10 mg/kg, i.p.) no NF, com o intuito de reverter tais alteraÃÃes comportamentais provocadas pela retirada forÃada do tratamento subcrÃnico com cocaÃna. Para o estudo neuroquÃmico (neuroadaptaÃÃo) foi utlizado o corpo estriado (CE) de ratos, avaliando-se os seguintes parÃmetros: nÃveis de monoaminas (NA, DA, 5-HT) e seus metabÃlitos (DOPAC, HVA e 5-HIAA) atravÃs do HPLC com detecÃÃo eletroquÃmica e a atividade da enzima catalase. Na avaliaÃÃo da ansiedade, os resultados mostraram que no LCE houve uma reduÃÃo do NEBA, PEBA, TPBA e PTBA na abstinÃncia de 24h e 7 d, apÃs 21d nÃo houve alteraÃÃo. No CA, as retiradas de 24h e 7 d promoveram um aumento da atividade locomotora do animal, no entanto na retirada de 21 d ocorreu uma diminuiÃÃo da atividade locomotora. Na abstinÃncia de 24h foram administrados propranolol, ondansetrom e buspirona. No LCE, o propranolol aumentou o NEBA e reduziu o PTBA, enquanto que o ondansetrom aumentou o NEBA, PEBA, TPBA e o PTBA em relaÃÃo ao grupo da cocaÃna. Jà a buspirona em relaÃÃo à cocaÃna aumentou o PTBA, TPBA e o PEBA, porÃm o NEBA foi reduzido. Enquanto que no CA, o propranolol, o ondansetrom e a buspirona reduziram a atividade locomotora em relaÃÃo ao grupo da cocaÃna. Para avaliar a atividade antidepressiva foi realizado o teste do nado forÃado, no qual as retiradas de 24h e 7 d reduziram o tempo de imobilidade, contudo na abstinÃncia de 21 d houve um aumento do parÃmetro avaliado. Na abstinÃncia de 21 d foram administrados paroxetina e bupropiona, verificando uma reduÃÃo do tempo de imobilidade em relaÃÃo ao grupo da cocaÃna. Para a realizaÃÃo dos estudos neuroquÃmicos, os animais foram dissecados para retirada do CE. No corpo estriado observou-se um aumento de dopamina (DA) e uma reduÃÃo de seus metabÃlitos (DOPAC e HVA) nas trÃs retiradas. A concentraÃÃo de serotonina aumentou nas trÃs retiradas, entretanto o seu metabÃlito (5HIAA) aumentou somente nas retiradas de 24h e 7d. Jà a noradrenalina reduziu apÃs as trÃs retiradas. Em relaÃÃo aos receptores, no corpo estriado D2 encontrava-se elevado em 24h e 7d, jà 5HT2 apÃs 7d e D1 nÃo foi alterado. Foi tambÃm avaliado no CE a atividade da catalase, enzima antioxidante, que mostrou uma reduÃÃo de sua atividade nas trÃs retiradas. Os resultados sugerem que diferentes perÃodos de retirada apÃs tratamento subcrÃnico com cocaÃna causam efeitos ansiogÃnicos e depressores sobre o SNC e tais efeitos foram revertidos por propranolol, ondansetrom, buspirona, bupropiona e paroxetina. O estudo neuroquÃmico mostrou que a abstinÃncia de cocaÃna sÃo eventos multimediados e que CE tem uma importante participaÃÃo, estando tambÃm a atividade da catalase envolvida neste processo. Estes achados sÃo importantes para a investigaÃÃo de novos tratamentos para a sÃndrome de abstinÃncia de cocaÃna. / Cocaine is world used and considered as a public health problem, being the relapse one of the hardly difficulties faced by cocaine users, that in the most cases, is related to abstinence symptoms, like anxiety, depression, irritability, fatigue and sleeplessness. To evaluate the behavioral alterations (anxiety and depression) and neurochemistry, rats were submitted to 24h, 7 d and 21 d withdrawal, after the subcronic treatment, for 7 days with cocaine (20mg/kg), being realized the experimental models of Elevated Plus Maze (EPM), Open Field (OF) and Forced Swimming (FS). Moreover, in the 24h abstinence, propranolol (10mg/kg, i.p.), ondansetrom (4mg/kg, i.p) and buspirone (5 mg/kg, i.p.) had been tested, in the EPM and OF, as wel as in the 21 d of abstinence bupropione (30mg/kg, i.p.) and paroxetine (10 mg/kg, i.p.) had been tested in the FS, aiming to revert the alterations caused by the abstinence of cocaine subcronic administration. For the neurochemistry study (neuroadaptation) was used striatum (ST) of rats, evaluating the following parameters: level of monoamines (NE, DA and 5HT) and its metabolites (DOPAC, HVA and 5HIAA), using the electrochemistry detection HPLC and the activity of the catalase enzyme. In the anxiety evaluation, results showed that in the EPM there was a reduction on NEOA, PEOA, TPOA and PTOA in the abstinence of 24h, 7 d and 21 d. In the OF, the withdrawal of 24 and 7 d promoted an increasing in the locomotor activity of animals, while the withdrawal of 21 d a decreasing in the locomotor activity was observed. In the 24h abstinence were administered propranolol, ondansetrom and buspirone. In the EPM, propranolol increased NEOA and reduced PTOA, while ondansetrom increased NEOA, PEOA, TPOA and PTOA, as compared to cocaine group. In addition buspirone as compared to cocaine group increased PTOA, TPOA, and PEOA, however NEOA was reduced. While in the OF, propranolol, ondansetron and buspirone reduced the locomotor activity as related to cocaine group. To evaluate the antidepressive effect the FS was performed, where the withdrawal of 24h and 7 d reduced the immobility time, although in the 21 d abstinence an increase of this parameter was observed. In the 21 d abstinence had been administered paroxetine and buproprione, verifying a reduction of the immobility time as related to cocaine group. To the performance of neurochemistry studies, animals were dissected to take off the ST. In the ST was observed an increasing of dopamine (DA) and a reduction of its metabolites (DOPAC and HVA) in the three withdrawals. The serotonine levels increased the three withdrawals, however its metabolite (5HIAA) increased only in the 24h and 7 d withdrawals. In addition norepinephrine reduced after the 24h, 7 d and 21 d withdrawal. In relation to the receptors, in the ST D2 24h and 7d met high in, already 5HT2 after 7d and D1 was not alteration. Were evaluated too in the ST the activity of catalase, antioxidant enzyme, that showed a reduction of your activity in the three withdrawal. Results suggests that different times of withdrawal after subcronic treatment with cocaine cause anxyogenic and depressive effects on the CNS and this effects were reverted by the administration of drugs (propranolol, ondansetrom, buspirone, bupropione and paroxetine). The neurochemistry study showed that the abstinence of cocaine were events multimediated and the brain area study ST has an important role, being the catalase activity involved in this process. These findings are important to the investigation of new treatments to the cocaine abstinence syndrome.

Ketamine is a non-competitive NMDA antagonist that has been shown to have antidepressant properties both clinically as well as in preclinical studies when administered at a subanesthetic dose. In vivo electrophysiological recordings were carried in male Sprague Dawley rats 30 minutes following ketamine administration (10 mg/kg) to first assess its effects on monoaminergic firing. Whilst no change in the firing activity of serotonin (5-HT) neurons was observed in the dorsal raphe nucleus (DRN), an increase in the firing activity was observed for dopamine (DA) and noradrenergic (NE) neurons in the ventral tegmental area (VTA) and locus coeruleus (LC), respectively. The effect of ketamine on these electrophysiological parameters was prevented by pre-administration of the AMPA receptor antagonist NBQX 10 minutes prior to ketamine administration. In a second series of experiments, an increase in AMPA-evoked response was observed within 30 minutes in the CA3 layer of the hippocampus (HPC) following acute ketamine administration. These findings suggest that acute ketamine administration produces a prompt enhancement of AMPA transmission in the forebrain and also results in increased catecholaminergic activity. These effects may play a crucial role in the rapid antidepressant effects of ketamine observed shortly following its infusion in the clinic.

No description available.

No description available.

Le carisbamate est la 1ère molécule à avoir un effet modificateur de l’épileptogenèse, dont environ 50% des animaux traités développent des crises d’absence, au lieu des crises limbiques normalement observées dans le modèle de la pilocarpine. Le principal objectif de cette thèse a été celui d’étudier les altérations qui se produisent par le traitement par le carisbamate. Pour cela nous avons effectué une cartographie de l’activité cérébrale, avec un immunomarquage de la protéine c-Fos, et nous avons vérifié les concentrations des monoamines et acides aminés dans l’hippocampe, le thalamus et dans le cortex piriforme par HPLC, 4h après le début du status epilepticus (SE). Enfin, nous avons vérifié le profil d’expression protéique dans l’hippocampe, 2 mois après le SE par électrophorèse bidimensionnelle.Les résultats indiquent que le carisbamate augmente l’activité des noyaux MD et LD du thalamus. Les résultats suggèrent aussi que la dopamine, la noradrenaline, le GABA et la sérotonine peuvent participer à la significative neuroprotection et à l’effet modificateur de l’épileptogenèse du carisbamate. L’étude de protéomique suggère également une réduction globale du métabolisme énergétique cellulaire chez les rats traité par le carisbamate qui développent des crises d’absence. / The carisbamate is the 1st molecule showing an epileptogenesis modifying effect, that about 50% of treated animals develops absence instead limbic seizures, commonly seen in the pilocarpine model. The aim of this thesis was to study the changes that follows carisbamate treatment. Therefore, we made a brain activity cartography, by labelling c-Fos protein, and we quantified the concentrations of amino acids and monoamines in hippocampus, thalamus and piriform cortex, 4h after the status epilepticus (SE). Moreover, we studied the protein expression profile in the hippocampus, 2 month after SE, by two-dimensional electrophoresis.The results points towards an increased activity of MD and LD thalamic nuclei in carisbamate treated rats. Furthermore, dopamine, noradrenaline, GABA and serotonin appears to play a role in neuroprotection and in the epileptogenesis modifying effect of carisbamate. The proteomic study revealed a global reduction of cellular energetic metabolism of carisbamate treated rats that develops absence seizures.