Papel do complexo receptor glutamato/NMDA e óxido nítrico no córtex pré-frontal medial na ansiedade de camundongos expostos ao labirinto em cruz elevado
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Data
2021-12-13
Autores
Silva, Ingrid Queiroz
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Universidade Estadual Paulista (Unesp)
Resumo
Medo e ansiedade são emoções decorrentes da resposta animal frente a estímulos ameaçadores ou perigosos, que resultam na exibição de reações de defesa. O estresse é um fator de risco para o desenvolvimento de diversos transtornos mentais, uma vez que não necessariamente todos os indivíduos expostos a um estressor desenvolvem as mesmas alterações comportamentais e fisiológicas. Desta forma, o Córtex Pré-Frontal medial (CPFm), um importante substrato neural que modula simultaneamente o estresse e a ansiedade, parece possuir lateralização funcional na execução das reações de defesa. Neste sentido, a estimulação do CPFm Direito (D) induz respostas ansiogênicas, enquanto o CPFm Esquerdo (E), quando ativado, as atenua. Além disso o óxido nítrico, sintetizado pela ativação de receptores glutamatérgicos do tipo NMDA, e o próprio NMDA (N-metil-D-aspartato – agonista glutamatérgico), parecem modular as reações de defesa induzidas ou não pelo estresse. A derrota social de um intruso por um coespecífico parece ser uma interessante ferramenta para explorar o efeito do estresse no contexto do CPFm. Portanto, o objetivo deste estudo foi investigar o papel do receptor glutamatérgico NMDA e dos neurotransmissores óxido nítrico e glutamato no córtex pré-frontal no comportamento defensivo de camundongos derrotados socialmente e/ ou expostos ao Labirinto em Cruz Elevado (LCE). Para isso, foi realizada (1) a avaliação dos efeitos da injeção de NMDA, em concentração sem efeito intrínseco na ansiedade (estabelecida por estudo piloto), no CPFm Esquerdo, em camundongos socialmente derrotados e expostos ao LCE; (2) avaliação dos efeitos da inibição da óxido nítrico sintase neuronal (NOSn), via injeção de intra-CPFm Direito de NPLA, no comportamento defensivo de camundongos expostos ao LCE. Os resultados demonstram que o protocolo usado para a exposição aguda ao estresse de derrota social não promoveu efeito ansiogênico. Além disso, a injeção de NPLA no CPFmD revelou um efeito ansiolítico em camundongos expostos ao LCE. Desta forma, esses resultados sugerem um envolvimento nitrérgico no CPFmD na modulação da ansiedade em camundongos expostos ao LCE.
Fear and anxiety are emotions arising from animal's response to threatening or dangerous stimuli which results in the display of defensive reactions. The stress is a risk factor for the development of various mental disorders, considering that not all individuals exposed to a stressor develop the same behavioral and physiological outcomes. Therefore, the medial prefrontal cortex, an important neural substrate that modulate stress and anxiety simultaneously seems to have functional lateralization in the execution of defensive reactions. Consequently, the stimulation of right (R) mPFC induces anxiogenic-like responses, in contrast to the left (L) mPFC that, when activated, reduce this anxiolytic effect. In addition, the nitric oxide that is synthesized by the activation of NMDA-type glutamatergic receptors, and the NMDA (N-metil-Daspartate – glutamatergic agonist) itself, seems to modulate the defensive reactions induced or not by the stress. The social defeat of an intruder by a conspecific seems to be an interesting tool to explore the effect of stress in the mPFC context. Therefore, the aim of this study was to investigate the role of the NMDA glutamatergic receptor and the neurotransmitters nitric oxide and glutamate in the prefrontal cortex in the defensive behavior of mice socially defeated and/or exposed to the elevated plus maze (EPM). Accordingly, it has been performed (1) the evaluation of the effects of NMDA injection, at an intrinsic-inactive dose in anxiety, in the Left mPFC, in mice socially defeated and exposed to EPM; (2) evaluation of the effects of neuronal nitric oxide synthase (nNOS) inhibition, through intra-RmPFC NPLA injections on the defensive behavior of mice exposed to EPM. The results demonstrate that the protocol used for acute exposure to social defeat stress did not promote anxiogenic-like effect. Furthermore, NPLA injection into the RmPFC showed an anxiolytic role in mice exposed to EPM. Thus, these results suggest a nitrergic involvement in right mPFC in the modulation of anxiety in mice exposed to EPM.
Fear and anxiety are emotions arising from animal's response to threatening or dangerous stimuli which results in the display of defensive reactions. The stress is a risk factor for the development of various mental disorders, considering that not all individuals exposed to a stressor develop the same behavioral and physiological outcomes. Therefore, the medial prefrontal cortex, an important neural substrate that modulate stress and anxiety simultaneously seems to have functional lateralization in the execution of defensive reactions. Consequently, the stimulation of right (R) mPFC induces anxiogenic-like responses, in contrast to the left (L) mPFC that, when activated, reduce this anxiolytic effect. In addition, the nitric oxide that is synthesized by the activation of NMDA-type glutamatergic receptors, and the NMDA (N-metil-Daspartate – glutamatergic agonist) itself, seems to modulate the defensive reactions induced or not by the stress. The social defeat of an intruder by a conspecific seems to be an interesting tool to explore the effect of stress in the mPFC context. Therefore, the aim of this study was to investigate the role of the NMDA glutamatergic receptor and the neurotransmitters nitric oxide and glutamate in the prefrontal cortex in the defensive behavior of mice socially defeated and/or exposed to the elevated plus maze (EPM). Accordingly, it has been performed (1) the evaluation of the effects of NMDA injection, at an intrinsic-inactive dose in anxiety, in the Left mPFC, in mice socially defeated and exposed to EPM; (2) evaluation of the effects of neuronal nitric oxide synthase (nNOS) inhibition, through intra-RmPFC NPLA injections on the defensive behavior of mice exposed to EPM. The results demonstrate that the protocol used for acute exposure to social defeat stress did not promote anxiogenic-like effect. Furthermore, NPLA injection into the RmPFC showed an anxiolytic role in mice exposed to EPM. Thus, these results suggest a nitrergic involvement in right mPFC in the modulation of anxiety in mice exposed to EPM.
Descrição
Palavras-chave
Ansiedade, Estresse, Córtex pré-frontal medial, Derrota Social, Anxiety, Stress, Medial Prefrontal Cortex, Social defeat