Caracterização comportamental, bioquímica e farmacológica do modelo de estresse crônico por restrição de movimentos com duração variável
Arquivos
Data
2019-08
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Estresse pode ser definido como qualquer estímulo que representa uma ameaça real ou
virtual a homeostase. Quando o estresse se torna crônico, há uma sobrecarga alostática
com consequências patológicas. O objetivo deste estudo foi caracterizar
comportalmente, bioquimicamente e farmacologicamente um novo modelo de estresse
crônico, baseado na restrição de movimentos com duração variável (2, 4 ou 6 h, em um
cronograma imprevisível) por for 3 semanas. Peso corporal, peso relativo da glândula
adrenal, níveis de corticoterona plasmática, citocinas cerebrais, sinaptofisina, serotonina
e dopamina, comportamento do tipo ansioso (supressão alimentar pela novidade,
labirinto em cruz elevado, e campo aberto), comportamento motivado (contraste negativo
de sacarose e teste do nado forçado) e comportamento social (investigação social e
interação social) foram avaliados após o protocolo de estresse crônico. A influência dos
neurotransmissores serotonina e dopamina no comportamento social foi também
avaliada através da administração aguda de diazepam, haloperidol e escitalopram.
Animais estressados mostraram menor ganho de peso corporal, maior peso relativo das
glândulas adrenais, niveis de citocinas hipocampais mais elevados, menores níveis de
serotonina no hipocampo, maiores níveis de dopamina e rotatividade de serotonina na
amigdala, supressão reduzida da solução de sacarose com baixa concentração e
aumento da imobilidade no teste do nado forçado, comportamento do tipo ansioso no
contexto social e maior agressividade. Tratamento agudo com escitalopram melhorou as
mudanças no comportamento social. Nós propomos o uso deste modelo como uma
ferramenta para o estudo das alterações induzidas pelo estresse crônico e possíveis
tratamentos para comportamentos indzidos pelo estresse crônico.
Stress can be defined as any stimulus that represents a real or virtual threat to homeostasis. When stress becomes chronic, there is an allostatic overload with pathological consequences. The main goal of this study was to characterize behaviorally, biochemically and pharmacologically a new model of chronic stress, based on movement restraint with variable duration (2, 4 or 6 h, in an unpredictable schedule) for 3 weeks. Body weight, relative weight of the adrenal glands, plasma corticosterone, brain cytokines, synaptophysin, serotonin and dopamine levels, anxiety-like (novelty suppressed feeding, elevated plus maze and open field test) motivated (sucrose negative contrast test and forced swimming test) and social behaviors (social investigation and social interaction) were assessed after the chronic protocol. The influence of serotonin and dopamine on social behavior was also evaluated through the acute administration of diazepam, haloperidol and escitalopram. Stressed animals showed lower body weight gain, higher relative weight of the adrenal gland, higher levels of hippocampal cytokines, lower hippocampal serotoin levels, higher dopamine and serotonin turnover levels in the amygdala, reduced suppression of low concentration sucrose solution and increased immobility in the forced swim test, anxiety-like behavior in social context and higher aggressiveness. Acute treatment with escitalopram improved social behavior changes. We propose the use of this model as a tool for the study of changes induced by chronic stress and possible treatments for chronic-stress induced behaviors.
Stress can be defined as any stimulus that represents a real or virtual threat to homeostasis. When stress becomes chronic, there is an allostatic overload with pathological consequences. The main goal of this study was to characterize behaviorally, biochemically and pharmacologically a new model of chronic stress, based on movement restraint with variable duration (2, 4 or 6 h, in an unpredictable schedule) for 3 weeks. Body weight, relative weight of the adrenal glands, plasma corticosterone, brain cytokines, synaptophysin, serotonin and dopamine levels, anxiety-like (novelty suppressed feeding, elevated plus maze and open field test) motivated (sucrose negative contrast test and forced swimming test) and social behaviors (social investigation and social interaction) were assessed after the chronic protocol. The influence of serotonin and dopamine on social behavior was also evaluated through the acute administration of diazepam, haloperidol and escitalopram. Stressed animals showed lower body weight gain, higher relative weight of the adrenal gland, higher levels of hippocampal cytokines, lower hippocampal serotoin levels, higher dopamine and serotonin turnover levels in the amygdala, reduced suppression of low concentration sucrose solution and increased immobility in the forced swim test, anxiety-like behavior in social context and higher aggressiveness. Acute treatment with escitalopram improved social behavior changes. We propose the use of this model as a tool for the study of changes induced by chronic stress and possible treatments for chronic-stress induced behaviors.