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O antagonismo do receptor de serotonina do tipo 7 da subst?ncia cinzenta periaquedutal dorsal reduz a ansiedade experimental basal, mas n?o aquela gerada pela retirada do etanol em ratosSilveira, Marana Ali 02 September 2014 (has links)
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Previous issue date: 2014-09-02 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Indiv?duos dependentes de etanol que diminuem ou interrompem a sua utiliza??o
podem apresentar a S?ndrome de Abstin?ncia do ?lcool, caracterizada por sinais e
sintomas desagrad?veis que favorecem a reca?da, dentre eles, a ansiedade. Por ser
uma droga psicotr?pica, o etanol ? capaz de promover mudan?as comportamentais
e neurofisiol?gicas, atuando sobre diversos sistemas de neurotransmiss?o, dentre
outros o sistema seroton?rgico, que vem sendo diretamente relacionado aos estados
aversivos, como ? o caso da ansiedade. O presente estudo teve por objetivo
investigar a participa??o do receptor de serotonina do tipo 7 (5-HT7) da subst?ncia
cinzenta periaquedutal dorsal (DPAG) na ansiedade experimental basal e naquela
gerada pela retirada de etanol. Para isso, ratos Wistar com 75-100 dias foram
submetidos a dois experimentos. No primeiro, os animais receberam as doses de
2,5; 5,0 e 10 nmoles do antagonista de receptor 5-HT7 SB269970(SB) ou ve?culo
intra-DPAG e, dez minutos ap?s, foram expostos ao labirinto em cruz elevado (LCE).
No dia seguinte, os animais foram submetidos aos mesmos tratamentos e testados
no campo aberto (CA). No segundo experimento, os animais receberam
concentra??es crescentes (2%, 4%, 6%) de etanol como ?nica fonte de dieta l?quida
ou ?gua (grupo controle), ambos com acesso livre ? ra??o. Setenta e duas e noventa
e seis horas ap?s a retirada do etanol, os animais receberam SB (2,5 e 5,0 nmoles)
intra-DPAG dez minutos anteriores ao teste no LCE e no CA, respectivamente. No
experimento 1, a dose do antagonista de 10 nmoles foi capaz de reverter a
ansiedade gerada pela exposi??o ao LCE. No experimento 2, as doses ineficazes no
LCE de SB (2,5 e 5,0 nmoles) n?o foram capazes de reverter a ansiedade gerada
pela retirada de etanol no LCE, embora a dose de 2,5 nmoles de SB tenha revertido
o seu efeito hipolocomotor neste teste. Esses resultados sugerem que o receptor 5-
HT7 participa modulando a ansiedade experimental basal de ratos, mas n?o a
ansiedade gerada pela retirada do etanol na DPAG. / Ethanol-dependent individuals who reduce or discontinue its use may present
Alcohol Withdrawal Syndrome, which is characterized by unpleasant signs and
symptoms, such as anxiety, that may trigger relapses. Ethanol, a psychotropic drug,
is able to promote behavioral and neurophysiological changes, acting on different
neurotransmitter systems, including the serotonergic, which has also been directly
associated with aversive states, including anxiety. This study aimed to investigate the
participation of type 7 serotonin receptor (5-HT7) of the dorsal periaqueductal gray
(DPAG) on basal experimental anxiety and that caused by ethanol withdrawal. For
this, 75-100 days old Wistar rats were subjected to two experiments. On the first one,
animals underwent stereotactic surgery for implantation of guide cannulas used for
administration of the drug directly into the DPAG. After seven days, the animals
received doses of 2.5; 5 and 10 nmols of type 7 receptor antagonist SB269970 (SB)
or vehicle intra-DPAG and, ten minutes after, they were exposed to elevated plus
maze (EPM). In the following day, the animals were submitted to the same treatment
and tested in the open field (OF). In the second experiment, animals received
increasing concentrations (2%, 4%, 6%) of ethanol as the only source of liquid diet or
water (control group), both with free access to chow. Seventy two hours and ninety
six hours after the ethanol withdrawal, animals received SB (2.5 and 5.0 nmols) intraDPAG
ten minutes before the test in the LCE and OF, respectively. In experiment 1,
the dose of antagonist 10 nmols was able of reversing the anxiety generated by
EPM. In the experiment 2, ineffective SB doses on the LCE (2.5 and 5.0 nmol) were
not able to reverse the anxiety caused by the ethanol withdrawal in the EPM,
although the dose of 2.5 nmols of SB has reversed its hipolocomotor effect in this
test. This result suggests that the 5-HT7 receptor is involved in the modulation of the
basal experimental anxiety in rats, but not in the anxiety caused by ethanol
withdrawal in the DPAG.
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Avalia??o dos efeitos da retirada do etanol em curto e longo prazo sobre respostas comportamentais relacionadas ? ansiedade e sobre c?lulas imunorreativas para a serotonina no n?cleo dorsal da Rafe em ratasSantos, Raliny Oliveira 11 August 2014 (has links)
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Previous issue date: 2014-08-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Indiv?duos dependentes de etanol, ao reduzirem ou cessarem seu consumo,
apresentam um conjunto de sinais e sintomas, dentre eles, alguns relacionados ?
ansiedade. Para um melhor entendimento das bases neurais envolvidas com a
ansiedade na abstin?ncia, ensaios pr?-cl?nicos v?m utilizando modelos de consumo
de etanol seguido de retirada em ratos submetidos a distintos testes de ansiedade,
dentre eles, o labirinto em cruz elevado. O presente estudo teve por objetivo
investigar se a retirada do etanol em curto e longo prazo promoveria altera??es
comportamentais sugestivas de ansiedade no teste do labirinto em cruz elevado
(LCE) e no teste do campo aberto (CA) e, ainda, se influenciaria o n?mero de c?lulas
imunorreativas para a serotonina (5-HT-IR) no n?cleo dorsal da rafe (NDR), fonte de
inerva??o seroton?rgica ascendente relacionada ? ansiedade. Ratas Wistar com
aproximadamente 90 dias de vida foram submetidas a concentra??es crescentes de
etanol como ?nica fonte de dieta l?quida (2% durante os tr?s primeiros dias, seguido
de 4% durante tr?s dias e 6% durante 15 dias) ou ?gua (grupo controle), ambos com
livre acesso ? ra??o. Na etapa comportamental, no 21? dia de consumo, o etanol foi
substitu?do por ?gua (retirada) e, ap?s 72 horas ou 21 dias de retirada, os animais
controle e submetidos ? retirada foram expostos ao teste do LCE, onde foram
avaliadas as porcentagens de tempo gasto e de entradas nos bra?os abertos e o
n?mero de entradas nos bra?os fechados durante 5 minutos. Vinte e quatro horas
ap?s o teste no LCE, os animais foram submetidos ao teste do CA por 15 minutos.
Durante este per?odo avaliou-se a dist?ncia total percorrida pelos animais e durante
os 5 minutos iniciais foram avaliados o tempo, a dist?ncia e o n?mero de entradas
no centro do aparato. Na etapa imunoistoqu?mica, os enc?falos de animais
submetidos ao consumo de etanol por 21 dias, seguidos ou n?o de retirada de 72
horas e 21 dias, e seus controles foram submetidos ? t?cnica da imunoistoqu?mica
para detectar c?lulas 5-HT-IR nas por??es dorsal e caudal do NDR. Os dados
comportamentais mostraram que tanto a retirada do etanol em curto prazo, quanto
em longo prazo diminuiu a explora??o dos bra?os abertos do LCE. No teste do CA
n?o foram observadas altera??es na locomo??o no per?odo de 15 minutos; por?m,
no mesmo teste, durante os 5 primeiros minutos observou-se efeito do tipo
ansiog?nico nos animais submetidos ? 22 dias de retirada do etanol. Na etapa
imunoistoqu?mica, n?o foram observadas diferen?as na contagem de c?lulas 5-HTIR
nas por??es dorsal e caudal do NDR dos animais submetidos ? retirada em curto
e longo prazo do etanol, em rela??o ao controle. No entanto, o consumo do etanol
por 21 dias reduziu a contagem de c?lulas 5-HT-IR na regi?o dorsal deste n?cleo.
Em conjunto, os dados aqui obtidos demonstram um efeito do tipo ansiog?nico
promovido pela retirada em curto e longo prazo do etanol n?o relacionado a
altera??es na marca??o de serotonina nas por??es dorsal e caudal do NDR. / Ethanol withdrawn individuals present a wealth of signs and symptoms, some of
them related with anxiety. To better understand brain areas involved in anxiety
caused by ethanol abstinence, preclinical studies have been employing models of
ethanol consumption followed by withdrawal in rodents submitted to behavioral tests
of anxiety, such as the elevated plus-maze. The aim of this study was to investigate if
short- or long-term ethanol withdrawal could alter both anxiety-related behaviors in
the elevated plus-maze (EPM) and open field tests and the number of serotonin
immunorreactive cels in the dorsal raphe nucleus, a midbrain area associated with
anxiety. Female Wistar rats (90 days old) were submitted to increasing
concentrations of ethanol (2% for 3 days, 4% for 3 days and 6% for 15 days) as the
only source of liquid diet and the control group received water ad libitum. Both groups
received food ad libitum. In the behavioral experiments, on 21st day of consumption,
ethanol was substituted by water (withdrawal) and 72 h or 21 days after withdrawal
animals were submitted to the EPM, where it was evaluated the percentage of time
and entries in the open arms and the entries in the enclosed arms during 5 minutes.
Twenty and four hours after testing in the EPM, animals were submitted to the open
field test for 15 minutes, where the distance traveled by the animals was observed
along this period. During the first 5 minutes, the distance traveled, entries and time
spent in the center of the test were analyzed. In the immunohistochemistry study,
animals were submitted to 21 days of consumption of ethanol followed or not by 72
hours and 21 days of withdrawal previously perfusion, brain tissue preparation and
quantification of serotonin dyed cells in the dorsal and caudal portions in the dorsal
raphe nucleus. Behavioral data showed that both short- and long-term ethanol
withdrawals reduced the open arms exploration in the EPM. In the open field test
there were no locomotor activity changes during the total 15 minutes; however, longterm
ethanol withdrawal reduced the exploration in the center of the open field during
the first 5 minutes. In the immunohistochemistry step, there were no differences,
when short- and long-term withdrawn groups were compared with control group;
nevertheless, the chronic consumption of ethanol decreased the number of
serotonergic immunorreactive cells in the dorsal part of dorsal raphe nucleus. Taken
together, results here obtained suggest that both short- and long-term ethanol
withdrawals promoted an anxiogenic-like effect that was not related with changes in
the serotonin immunorreactivity in the dorsal and caudal parts of the dorsal raphe
nucleus.
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