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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

THE ROLE OF THE D3 DOPAMINE RECEPTOR IN RODENT BEHAVIORAL RESPONSES TO NOVELTY AND PSYCHOSTIMULANTS

PRITCHARD, LAUREL M. 05 October 2004 (has links)
No description available.
12

The Effects of Septal, Thalamic, and Tegmental Lesions on Locomotor Activity in the Hooded Rat

Dirlam, David Kirk 05 1900 (has links)
Animals with one of septal, medial thalamic or tegmental reticular formation lesions were compared on three measures of spontaneous activity (a brief test in a novel maze and seven-day tests in running wheels or photocells cages) and on active avoidance learning. Wheel running was depressed by all the lesions (especially septal and tegmental lesions) while locomotion in the maze and photocell cages was unaffected. Avoidance learning was depressed by septal and thalamic lesions but not by tegmental lesions. These results are discussed in terms of the hypothesis that these brain structures form part of systems which facilitate or inhibit somatomotor activity. / Thesis / Master of Arts (MA)
13

Lesions of the Dorsal Medial Hippocampus induce different forms of Repetitive Behaviour in the rat

Haq, Sahina January 2015 (has links)
The dorsal dentate gyrus (DDG) of the hippocampus plays a role in the expression of different forms of flexible behaviour mainly due to its ability to sustain neurogenesis throughout life. In the present thesis, we examined the role that the DDG and its adjacent areas, both collectively referred to as dorsal medial hippocampus (DMH), play in flexible, adaptive behaviour and cognitive processing. We used the neurotoxin, colchicine, to induce lesions of the DDG, which were found to affect neighbouring areas. Thus these lesions will be referred to as lesions of the DMH. In the first experiment, rats were tested for (1) perseverative behaviour before and after receiving chronic methamphetamine (METH) treatment, (2) METH-induced locomotor activity and stereotypy in an open field, and (3) working memory in a T-maze. The results showed that rats with lesions of the DMH exhibited perseveration and supersensitivity to the locomotor- and stereotypy-inducing effects of METH (0, 0.1, 0.3, 1 mg/kg i.p.) as well as increased long-term METH sensitization. Rats with DMH lesions also showed significant working memory deficits. Taken together, these results reveal specific forms of behavioural inflexibility in rats with lesions of the DMH that are mainly associated with perseveration, drug-related behaviours, including stimulant motor supersensitivity and drug sensitization, and impaired working memory functions.
14

Cannabinoid Modulation of Reinforcement Maintained by Stimulation of the Medial Forebrain Bundle in C57Bl/6J Mice

Wiebelhaus, Jason 20 September 2013 (has links)
Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain.
15

Seasonal variations in general activity, behaviour and cutaneous glandular structures in reindeer (Rangifer tarandus L.)

Mossing, Torgny January 1980 (has links)
The locomotor activity of the reindeer is separated into a diurnal and a nocturnal phase which, in turn, consists of a  number of short-term activity bursts. The onset and termination  of diurnal and nocturnal activity are largely in synchrony  with sunrise and sunset. Since the diurnal phase is  longer, total activity is dependent on the photoperiod. Total  activity as well as the number of activity bursts is greater  in Jùne with continuous daylight than in December with 6  hours daylight. In winter, reindeer spent less time feeding  but more time ruminating and resting *than in summer. Synchronization  between individuals was also greatest in winter. It  is concluded that the described changes in the activity  pattern are due to an endogenous component and that this component  further controls food consumption and energy balance  of the reindeer.  Seasonal variations in behavioural patterns are described.  Several specific rutting behavioürs, sexual and agonostic,  emerge in the male during the prerut and persist until after  the rut. The preorbital gland is enlarged and secretory activity  is evident. The rut is cha'tabterized by the sudden appearance  of an odour in the breath of mature males followed a few  later by a strong odour in the urine. These odours persist for  a short time during the most intense period of rut. The amount  of androgen rizes sharply and reaches peak concentrations in  late September - early October, decreasing thereafter. The  described behavioural cues occur with a certain constancy in  time in concecutive seasons.  A quantification of the amounts of secretory epithelia in preorbital,  interdigital, caudal and tarsal glands reveals that  only the preorbital gland is subjected to any seasonal and  sexual variation. The apocrine epithelium in this gland is  most developed in mature males during the rutting season and  seems to be dependent upon the presence of an elevated androgen  concentration. The tarsal gland is the least developed  gland while the interdigital and caudal glands are more welldeveloped  and structurally complex. Scattered apocrine glands  are only developed on the legs, the ventral body, oral angle  and in the rump patch. / digitalisering@umu
16

Análise da atividade locomotora de Aedes aegypti e Aedes albopictus (Diptera: Culicidae) do Parque Municipal do Piqueri São Paulo, SP / Analysis of the locomotor activity of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) of the Piqueri Municipal Park São Paulo, SP

Pancetti, Filipe Gabriel Menezes 23 August 2017 (has links)
O estudo de mosquitos é extremamente importante, pois muitos são considerados vetores de diversos patógenos transmissíveis ao homem. Aedes aegypti e Aedes albopictus são responsáveis por transmitir arbovírus, como os da dengue, chikungunya, zika e febre amarela urbana, no mundo. Neste trabalho foram empregados Ae. aegypti e Ae. albopictus para: analisar a atividade locomotora de machos, fêmeas virgens e fêmeas inseminadas naturalmente; comparar a atividade locomotora de fêmeas injetadas intratoracicamente com extrato de glândulas acessórias (AG) de machos co e heteroespecíficos; e verificar a taxa de inseminação de fêmeas injetadas com glândulas acessórias de machos co e heteroespecíficos, quando são posteriormente expostas a seus machos coespecíficos. Os mosquitos foram coletados em ovitrampas instaladas no Parque Municipal do Piqueri, Zona Leste da cidade de São Paulo, durante o outono e a primavera de 2015 e outono de 2016. Após a emergência dos adultos, estes foram transferidos para quatro gaiolas matrizes separadas por espécie e sexo, dos quais obtivemos machos e fêmeas virgens de cada espécie. Em outras duas gaiolas foram agrupadas por espécie, 40 fêmeas e 40 machos para cópula por 24 horas para obtermos fêmeas inseminadas naturalmente. Posteriormente, todos os mosquitos foram transferidos para uma incubadora por quatro dias para análise da atividade locomotora. Na comparação de fêmeas injetadas com glândulas acessórias, foram extraídas as glândulas de machos de Ae. aegypti e Ae. albopictus e estas injetadas intratoracicamente em fêmeas co e heteroespecíficas. Todas as fêmeas injetadas foram transferidas para uma incubadora por três dias. Para a análise dos dados foram utilizados os testes estatísticos F e T e ANOVA. Após a atividade locomotora, as fêmeas injetadas foram expostas a seus machos coespecíficos e posteriormente tiveram suas espermatecas dissecadas para verificar a presença de espermatozoides a fim de analisar a taxa de inseminação. Nos machos, fêmeas virgens e fêmeas inseminadas naturalmente de Ae. aegypti e Ae. albopictus, o padrão da atividade locomotora foi diurno e bimodal no outono e na primavera. Em Ae. aegypti machos a atividade foi mais evidente no outono e em Ae. albopictus na primavera. Nas fêmeas de Ae. aegypti virgens a atividade foi mais evidente que nas inseminadas naturalmente em ambas as estações. Nas fêmeas de Ae. albopictus não houve diferença na atividade das virgens e inseminadas. Nas fêmeas de Ae. aegypti injetadas com AG a atividade locomotora foi diurna, com padrão unimodal e menos marcada. Nas fêmeas de Ae. albopictus injetadas com AG não houve diferença. Na taxa de inseminação, somente Ae. albopictus fêmeas injetadas com AG heteroespecíficas apresentaram espermatozoides após cópula coespecífica. Este estudo contribui para compreensão do comportamento de mosquitos vetores como Ae. aegypti e Ae. albopictus / The study of mosquitoes is extremely important, since many are considered vectors of several pathogens transmissible to man. Aedes aegypti and Aedes albopictus are responsible for transmitting arboviruses, such as dengue, chikungunya, zika and urban yellow fever, in the world. This study employed Ae. aegypti and Ae. albopictus to: analyze the locomotor activity of males, virgin females and females naturally inseminated; compare the locomotor activity of females injected intratoracically with extract of accessory glands (AG) of co and heterospecific males; and verify the rate of insemination of females injected with accessory glands of co and heterospecific males when later exposed to their co-specific males. The mosquitoes were collected in ovitraps installed in Piqueri Municipal Park, East of São Paulo city, during the autumn and spring of 2015 and autumn of 2016. After the emergence of adults, they were transferred to four cages, separated by species and sex from which we obtained virgin males and females of each species. In the other two cages, they were grouped by species, 40 females and 40 males for mating during 24 hours to obtain naturally inseminated females. Thereafter, all the mosquitoes were transferred to an incubator for four days to the locomotor activity analysis. In the comparison of females injected with accessory glands, the male glands of Ae. aegypti and Ae. albopictus were extracted and injected intratoracically into co and heterospecific females. All injected females were transferred to an incubator for three days. For the analysis, the statistical tests F and T and ANOVA were used. After the locomotor activity, the injected females were exposed to their co-specific males and later had their spermathecas dissected to verify the presence of spermatozoa in order to analyze the insemination rate. In males, virgin and naturally inseminated females of Ae. aegypti and Ae. albopictus, the pattern of locomotor activity was diurnal and bimodal in autumn and spring. Aedes aegypti males activity was more evident in autumn and in Ae. albopictus in spring. In virgin females of Ae. aegypti the activity was more evident than in the naturally inseminated in both seasons. In females of Ae. albopictus, there was no difference in the activity of virgin and inseminated. In females of Ae. aegypti injected with AG the locomotor activity was diurnal, with a unimodal and less marked pattern. In the females of Ae. albopictus injected with AG there was no difference. In the insemination rate, only Ae. albopictus females injected with heterospecific AGs presented spermatozoa after coespecific mating. This study contributes to the understanding of mosquito vectors behavior such as Ae. aegypti and Ae. albopictus
17

Análise da atividade locomotora de Aedes aegypti e Aedes albopictus (Diptera: Culicidae) do Parque Municipal do Piqueri São Paulo, SP / Analysis of the locomotor activity of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) of the Piqueri Municipal Park São Paulo, SP

Filipe Gabriel Menezes Pancetti 23 August 2017 (has links)
O estudo de mosquitos é extremamente importante, pois muitos são considerados vetores de diversos patógenos transmissíveis ao homem. Aedes aegypti e Aedes albopictus são responsáveis por transmitir arbovírus, como os da dengue, chikungunya, zika e febre amarela urbana, no mundo. Neste trabalho foram empregados Ae. aegypti e Ae. albopictus para: analisar a atividade locomotora de machos, fêmeas virgens e fêmeas inseminadas naturalmente; comparar a atividade locomotora de fêmeas injetadas intratoracicamente com extrato de glândulas acessórias (AG) de machos co e heteroespecíficos; e verificar a taxa de inseminação de fêmeas injetadas com glândulas acessórias de machos co e heteroespecíficos, quando são posteriormente expostas a seus machos coespecíficos. Os mosquitos foram coletados em ovitrampas instaladas no Parque Municipal do Piqueri, Zona Leste da cidade de São Paulo, durante o outono e a primavera de 2015 e outono de 2016. Após a emergência dos adultos, estes foram transferidos para quatro gaiolas matrizes separadas por espécie e sexo, dos quais obtivemos machos e fêmeas virgens de cada espécie. Em outras duas gaiolas foram agrupadas por espécie, 40 fêmeas e 40 machos para cópula por 24 horas para obtermos fêmeas inseminadas naturalmente. Posteriormente, todos os mosquitos foram transferidos para uma incubadora por quatro dias para análise da atividade locomotora. Na comparação de fêmeas injetadas com glândulas acessórias, foram extraídas as glândulas de machos de Ae. aegypti e Ae. albopictus e estas injetadas intratoracicamente em fêmeas co e heteroespecíficas. Todas as fêmeas injetadas foram transferidas para uma incubadora por três dias. Para a análise dos dados foram utilizados os testes estatísticos F e T e ANOVA. Após a atividade locomotora, as fêmeas injetadas foram expostas a seus machos coespecíficos e posteriormente tiveram suas espermatecas dissecadas para verificar a presença de espermatozoides a fim de analisar a taxa de inseminação. Nos machos, fêmeas virgens e fêmeas inseminadas naturalmente de Ae. aegypti e Ae. albopictus, o padrão da atividade locomotora foi diurno e bimodal no outono e na primavera. Em Ae. aegypti machos a atividade foi mais evidente no outono e em Ae. albopictus na primavera. Nas fêmeas de Ae. aegypti virgens a atividade foi mais evidente que nas inseminadas naturalmente em ambas as estações. Nas fêmeas de Ae. albopictus não houve diferença na atividade das virgens e inseminadas. Nas fêmeas de Ae. aegypti injetadas com AG a atividade locomotora foi diurna, com padrão unimodal e menos marcada. Nas fêmeas de Ae. albopictus injetadas com AG não houve diferença. Na taxa de inseminação, somente Ae. albopictus fêmeas injetadas com AG heteroespecíficas apresentaram espermatozoides após cópula coespecífica. Este estudo contribui para compreensão do comportamento de mosquitos vetores como Ae. aegypti e Ae. albopictus / The study of mosquitoes is extremely important, since many are considered vectors of several pathogens transmissible to man. Aedes aegypti and Aedes albopictus are responsible for transmitting arboviruses, such as dengue, chikungunya, zika and urban yellow fever, in the world. This study employed Ae. aegypti and Ae. albopictus to: analyze the locomotor activity of males, virgin females and females naturally inseminated; compare the locomotor activity of females injected intratoracically with extract of accessory glands (AG) of co and heterospecific males; and verify the rate of insemination of females injected with accessory glands of co and heterospecific males when later exposed to their co-specific males. The mosquitoes were collected in ovitraps installed in Piqueri Municipal Park, East of São Paulo city, during the autumn and spring of 2015 and autumn of 2016. After the emergence of adults, they were transferred to four cages, separated by species and sex from which we obtained virgin males and females of each species. In the other two cages, they were grouped by species, 40 females and 40 males for mating during 24 hours to obtain naturally inseminated females. Thereafter, all the mosquitoes were transferred to an incubator for four days to the locomotor activity analysis. In the comparison of females injected with accessory glands, the male glands of Ae. aegypti and Ae. albopictus were extracted and injected intratoracically into co and heterospecific females. All injected females were transferred to an incubator for three days. For the analysis, the statistical tests F and T and ANOVA were used. After the locomotor activity, the injected females were exposed to their co-specific males and later had their spermathecas dissected to verify the presence of spermatozoa in order to analyze the insemination rate. In males, virgin and naturally inseminated females of Ae. aegypti and Ae. albopictus, the pattern of locomotor activity was diurnal and bimodal in autumn and spring. Aedes aegypti males activity was more evident in autumn and in Ae. albopictus in spring. In virgin females of Ae. aegypti the activity was more evident than in the naturally inseminated in both seasons. In females of Ae. albopictus, there was no difference in the activity of virgin and inseminated. In females of Ae. aegypti injected with AG the locomotor activity was diurnal, with a unimodal and less marked pattern. In the females of Ae. albopictus injected with AG there was no difference. In the insemination rate, only Ae. albopictus females injected with heterospecific AGs presented spermatozoa after coespecific mating. This study contributes to the understanding of mosquito vectors behavior such as Ae. aegypti and Ae. albopictus
18

Efeitos da exposição combinada de cafeína e etanol durante o desenvolvimento na atividade locomotora de camundongos adolescentes / Effects of combined exposure of caffeine and ethanol during development in locomotor activity of adolescent mice

Ana Cristina Chagas Carvalho da Silva 26 February 2014 (has links)
Conselho Nacional de Desenvolvimento Científico e Tecnológico / O Transtorno do Déficit de Atenção e Hiperatividade (TDAH) é uma desordem neurocomportamental caracterizada por graus variados de desatenção, atividade motora excessiva e impulsividade. Sua etiologia não é completamente conhecida, porém, um grande número de evidências sugere que, além de fatores de risco genéticos, a exposição gestacional ao etanol e a altas doses de cafeína contribuem para a manifestação deste transtorno. O etanol, presente na composição de bebidas alcoólicas, e a cafeína, presente na composição de diversas bebidas (refrigerantes, chás, café, e energéticos), alimentos derivados do cacau e medicamentos estão entre as substâncias neuroativas mais consumidas no mundo. Apesar das evidências epidemiológicas do uso combinado de cafeína e etanol por gestantes, as interações entre estas substâncias têm recebido pouca atenção em estudos experimentais. Este fato é particularmente importante visto que alguns estudos apontam que cafeína é capaz de ampliar alguns aspectos importantes da ação de outras substâncias com potencial neurotóxico. Nesse estudo avaliamos os efeitos da co-exposição à cafeína e ao etanol durante o desenvolvimento na atividade locomotora em camundongos adolescentes. Para tanto, camundongos Suíços foram expostos do primeiro dia gestacional até o vigésimo primeiro dia pós-natal (PN21), a solução de cafeína 0,1g/L (Grupo CAF1, 10 ninhadas), a solução de cafeína 0,3g/L (Grupo CAF3, 10 ninhadas) ou tiveram acesso à água potável (Grupo CAF0, 10 ninhadas). Em dias alternados de PN2 a PN8, os animais de cada ninhada receberam uma injeção intraperitoneal de 0,25 l/g de etanol (grupo ETOH25), 0,5 l/g de etanol (grupo ETOH50) ou de solução salina (grupo ETOH0). Em PN30, a atividade locomotora foi avaliada por 15 minutos no teste de Campo Aberto. A análise dos níveis de etanol sérico, realizada em uma amostra independente de animais em PN8, indicou que, para as duas doses de etanol, a alcoolemia dos animais do grupo CAF3 foi significativamente maior do que as dos grupos CAF0 e CAF1, que não diferiram entre si. No teste de campo aberto, apenas os animais expostos ao etanol apresentaram aumento da atividade locomotora. Tanto o grupo ETOH25 quanto o grupo ETOH50 tiveram a atividade maior que o grupo ETOH0. A exposição à cafeína, por si só, não afetou a atividade locomotora dos animais nem potencializou os efeitos do etanol. No grupo CAF3, a atividade locomotora não foi afetada pela exposição ao etanol. Nossos dados confirmam o papel da exposição precoce ao etanol na manifestação da hiperatividade locomotora. Além disso, a exposição à cafeína durante o desenvolvimento pode exercer um papel protetor para a manifestação da hiperatividade locomotora induzida pela exposição precoce ao etanol. / The attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by varying degrees of inattention, excessive motor activity and impulsivity. This etiology is not fully known, but considerable evidence suggests that, in addition to genetic factors, exposure to ethanol and high doses of caffeine contribute to the manifestation of the disorder. Ethanol, which is present in all alcoholic beverages, and caffeine, which is present in many beverages (sodas, teas, coffee and energetic drinks), food derived from cacao and medications, are two of the most consumed neuroactive drugs in the world. In spite of the epidemiological evidence of the combined use of caffeine and ethanol by pregnant women, the interactions between these two drugs have received little attention in experimental studies. This fact is particularly important since some studies have shown that caffeine is capable of amplifying important aspects of the action of other substances that have neurotoxic potential. In the current study we analyzed the effects of co-exposure to caffeine and ethanol during development on the locomotor activity of pre-pubertal mice. In this sense, Swiss mice were exposed from the first gestational day to the 21st postnatal (PN21) day to one of three solutions: 1) a solution containing caffeine 0.1 g/L (group CAF1, 10 litters); 2) a solution containing caffeine 0.3g/L (group CAF3, 10 litters); 3) filtered tap water (group CAF0, 10 litters). Every other day, from PN2 to PN8, animals in each litter were i.p injected with one of the following solutions: 1) 0.25 l/g ethanol (group ETOH25); 2) 0.5 l/g ethanol (group ETOH50); 3) saline solution (group ETOH0). On PN30, locomotor activity was analyzed for 15 min in the open field. The analysis of the ethanol serum levels, which was carried out in an independent sample of animals at PN8, indicated that levels were significantly higher in the CAF3 group when compared to the other two groups, which did not differ between them. In the open field, the ethanol exposure caused a dose-dependent increase in the locomotor activity. The locomotor activity of the group ETOH0 was lower than that presented by the ETOH25 and the ETOH50 groups. The caffeine exposure was not capable of affecting the locomotor activity. In the group CAF3, the locomotor activity was not affected by the ethanol exposure. Our data corroborate previous studies in that it shows that precocious ethanol exposure results in locomotor hyperactivity. Furthermore, it is possible that caffeine exposure during development have a protective effect on deleterious effects of ethanol.
19

AGE-DEPENDENT EFFECTS OF EEDQ ON COCAINE-INDUCED LOCOMOTOR ACTIVITY AND D2 RECEPTOR SUPERSENSITIVITY

Teran, Angie 01 July 2019 (has links)
The neurochemical changes occurring between the preweanling period and adolescence could be crucial for understanding the role development plays in the manifestation of psychotic behaviors. N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) fully attenuates the DA agonist-induced behaviors of adult rats, while potentiating the DA agonist-induced locomotor activity of preweanling rats. My specific hypotheses were as follows: (1) Systemically administered EEDQ would block the cocaine-induced locomotor activity of adult rats. (2) Systemically administered EEDQ would potentiate the cocaine-induced locomotion of preweanling rats. (3) EEDQ would increase the Emax values (a measure of D2 receptor sensitivity) of preweanling rats, but not adolescent or adult rats. And, (4) EEDQ would reduce dorsal striatal β-arrestin-2 (ARRB2) and GRK6 levels (measures of D2 receptor sensitivity) of preweanling rats. Behavioral results were as expected, because EEDQ attenuated the locomotion of adult and adolescent rats, while EEDQ potentiated locomotor activity of preweanling rats. EEDQ enhanced the GTPγS binding of preweanling rats, while depressing ARRB2 levels. These results are consistent with the overarching hypothesis that EEDQ causes DA supersensitivity in preweanling rats. Thus, it is here proposed that EEDQ inactivates a significant number of D2 receptors in preweanling rats, but that the remaining D2 receptors are supersensitive and capable of mediating a potentiated locomotor response.
20

ACTIVATION OF HEME OXYGENASE-2 TO IMPROVE OUTCOME AFTER TRAUMATIC BRAIN INJURY

LEE, WALLACE 02 July 2014 (has links)
Traumatic brain injury (TBI) is an injury of the brain most often caused by blunt force trauma to the head and typically characterized by an increase in reactive oxygen species (ROS), inflammation, and hemorrhaging. Heme oxygenase (HO) catalyzes the breakdown of heme into carbon monoxide (CO), biliverdin which is further reduced to bilirubin, and ferrous iron. There are two active isoforms: HO-1 which is inducible and found predominantly in liver and spleen tissue; and HO-2 which is constitutive and found predominantly in the brain and testis. The metabolites of heme possess cytoprotective properties that can limit damage resulting from TBI. Our laboratory has found a selective HO-2 activator known as menadione (MD) that has been found to increase HO-2 activity by 4-fold while not affecting HO-1 in vitro. Given the higher amounts of HO-2 found in the brain and the cytoprotective properties of heme metabolites, we postulate that activation of HO-2 using menadione would mitigate further damage after TBI. The rat controlled cortical impact (CCI) model was used to simulate TBI with spontaneous locomotor activity (SLA), spontaneous alternation behaviour (SAB), and beam balance (BB) as the behavioural tasks to assess cognitive and motor function. A dose-response study (25, 50, 100, 200 μmol/kg) was performed to ascertain the effect of MD treatment on injured animals comparing to uninjured controls and injured animals treated with the vehicle (saline). We found that BB performance improved to control levels after MD treatment at 25 μmol/kg and 50 μmol/kg whereas animals treated with saline did not improve. SLA and SAB performance did not improve after treatment with MD. The findings suggest that HO-2 activation may be a viable method in mitigating further injury after TBI. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2014-06-27 19:33:45.645

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