Efeitos da cocaína crack sobre o comportamento de ratos no labirinto em T elevado e substratos neurais envolvidos
Data
2020-03-19
Autores
Rosário, Bárbara dos Anjos [UNIFESP]
Orientadores
Viana, Milena de Barros [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A cocaína crack, ou simplesmente crack, foi introduzida no Brasil no final da
década de 80, e seu uso tem aumentado drasticamente nos últimos anos para todos
os grupos socioeconômicos. Hoje, o Brasil é o segundo maior mercado do mundo
para a cocaína crack. Usuários de crack apresentam um pior prognóstico quando
comparados com usuários de outras drogas ilícitas porque a droga provoca um quadro
de dependência mais grave. A exposição repetida a drogas produz neuroadaptações
em regiões encefálicas relacionadas à recompensa que modulam tanto o
desenvolvimento do consumo compulsivo de drogas, quanto a recaída para a busca
de drogas durante a abstinência. Muitas destas neuroadaptações resultam da indução
de fatores de transcrição e subsequente regulação da expressão gênica. A família Fos
de fatores de transcrição é de particular interesse, já que os membros desta família
mostram padrões de indução diferencial em regiões encefálicas após exposição
aguda e crônica à cocaína. A retirada da droga produz aumento nos limiares de
recompensa e aumento nas respostas do tipo ansiosas. O presente trabalho
investigou os efeitos da exposição, em ratos Wistar machos, à cocaína crack após o
tratamento subcrônico por 5 dias e retirada da droga por 3 dias, sobre os padrões de
comportamento associados à ansiedade e ao pânico, através do modelo do labirinto
em T elevado (LTE). Para mensurar a atividade motora destes animais, eles foram
testados em um campo aberto. Além disso, foi avaliada a ativação dos substratos
neurais envolvidos com estes comportamentos para cada um dos dois grupos, através
da análise de imunoistoquímica à proteína Delta FosB. Os resultados mostraram que
nos animais submetidos ao tratamento subcrônico com a droga houve aumento das
latências de fuga no modelo do LTE, um efeito panicolítico, que foi acompanhado por
uma diminuição da ativação de estruturas relacionadas à modulação de respostas
relacionadas ao pânico. Já o período de três dias de retirada da droga não interferiu
significativamente com as tarefas comportamentais mensuradas no LTE, embora
tenha diminuído a ativação de estruturas críticas para a modulação de respostas
relacionadas à ansiedade e ao estresse. Esses resultados contribuem para o melhor
entendimento dos efeitos neurobiológicos da cocaína crack.
Crack cocaine, or simply crack, was introduced in Brazil in the late 1980s, and its use has increased dramatically in recent years for all socioeconomic groups. Today, Brazil is the second largest market in the world for crack cocaine. Crack users have a worse prognosis when compared to users of other illicit drugs because the drug causes a more severe dependency. Repeated exposure to drugs produces neuroadaptations in brain regions related to the reward that modulate both the development of compulsive drug use and the relapse to the search for drugs in abstinence. Many of these neuroadaptations result from the induction of transcription factors and subsequent regulation of gene expression. The Fos family of transcription factors is of particular interest, as members of this family show differential induction patterns in brain regions after acute and chronic exposure to cocaine. Drug withdrawal produces an increase in reward thresholds and an increase in anxiety-type responses. The present work investigates the effects of exposure, in male Wistar rats, to crack cocaine after subchronic treatment (for 5 days) and withdrawal of the drug (3 days), on behavioral patterns associated with anxiety and panic, through the use of the elevated T-maze (ETM). To measure the motor activity of these animals, they were subsequently tested in an open field. In addition, the activation of the neural substrates involved in these behaviors was evaluated for each of the two groups, through immunohistochemistry analysis to the Delta FosB protein. The results showed that in animals submitted to subchronic treatment with the drug, there was an increase in escape latencies in the ETM model, a panicolytic-like effect, which was accompanied by a decrease in the activation of structures related to the modulation of responses related to panic. The drug withdrawal period did not significantly interfere with the behavioral tasks measured in the ETM, although it decreased the activation of critical structures for the modulation of responses related to anxiety and stress. These results contribute to a better understanding of the neurobiological effects of crack cocaine
Crack cocaine, or simply crack, was introduced in Brazil in the late 1980s, and its use has increased dramatically in recent years for all socioeconomic groups. Today, Brazil is the second largest market in the world for crack cocaine. Crack users have a worse prognosis when compared to users of other illicit drugs because the drug causes a more severe dependency. Repeated exposure to drugs produces neuroadaptations in brain regions related to the reward that modulate both the development of compulsive drug use and the relapse to the search for drugs in abstinence. Many of these neuroadaptations result from the induction of transcription factors and subsequent regulation of gene expression. The Fos family of transcription factors is of particular interest, as members of this family show differential induction patterns in brain regions after acute and chronic exposure to cocaine. Drug withdrawal produces an increase in reward thresholds and an increase in anxiety-type responses. The present work investigates the effects of exposure, in male Wistar rats, to crack cocaine after subchronic treatment (for 5 days) and withdrawal of the drug (3 days), on behavioral patterns associated with anxiety and panic, through the use of the elevated T-maze (ETM). To measure the motor activity of these animals, they were subsequently tested in an open field. In addition, the activation of the neural substrates involved in these behaviors was evaluated for each of the two groups, through immunohistochemistry analysis to the Delta FosB protein. The results showed that in animals submitted to subchronic treatment with the drug, there was an increase in escape latencies in the ETM model, a panicolytic-like effect, which was accompanied by a decrease in the activation of structures related to the modulation of responses related to panic. The drug withdrawal period did not significantly interfere with the behavioral tasks measured in the ETM, although it decreased the activation of critical structures for the modulation of responses related to anxiety and stress. These results contribute to a better understanding of the neurobiological effects of crack cocaine
Descrição
Citação
ROSÁRIO, Bárbara dos Anjos. Efeitos da cocaína crack sobre o comportamento de ratos no labirinto em T elevado e substratos neurais envolvidos. 2020. 44 f. Dissertação (Mestrado Interdisciplinar em Ciências da Saúde) - Instituto de Saúde e Sociedade, Universidade Federal de São Paulo, Santos, 2020.