Role of nitric oxide in the periaqueductal gray in defensive behavior in mice: influence of prior local N-methyl-D-aspartate receptor activation and aversive condition

Glutamate N-methyl-D-aspartate (NMDA) receptor activation within the dorsal column of the periaqueductal gray (dPAG) leads to antinociceptive, autonomic, and behavioral responses characterized as the fear reaction. Activation of NMDA receptors in the brain increases nitric oxide (NO) synthesis, and NO has been proposed to be a mediator of the aversive action of glutamate. This paper reviews a series of studies investigating the effects of neuronal NO synthase (nNOS) inhibition in the dPAG of mice in different aversive conditions. nNOS inhibition by infusion of Nω-propyl-L-arginine (NPLA) prevents fear-like reactions (e.g., jumping, running, freezing) induced by NMDA receptor stimulation within the dPAG and produces anti-aversive effects when injected into the same midbrain site in mice confronted with a predator. Interestingly, nNOS inhibition within the dPAG does not change anxiety-like behavior in mice exposed to the elevated plus maze (EPM), but it reverses the effect of an anxiogenic dose of NMDA injected into the same site in animals subjected to the EPM. Altogether, the results support a role for glutamate NMDA receptors and NO in the dPAG in the regulation of defensive behaviors in mice. However, dPAG nitrergic modulation of anxiety-like behavior appears to depend on the magnitude of the aversive stimulus.

Papel da regiäo AV3V no choque séptico experimental em ratos tratados com NaCl 7, 5 / The role of AV3V region in experimental septic shock, in rats treated with NaCl 7, 5

Nossos resultados mostram que a soluçäo de NaCl7, 5 por cento (SH) possui açäo benéfica no choque circulatório produzido pela injeçäo endovenosa de endotoxina (Etx) em ratos, apresentando um restabelecimento parcial da pressäo média, sendo este efeito abolido em animais com lesäo AV3V. Porém, no choque circulatório severo, produzido por doses altas de Etx, a SH näo foi capaz de causar benefícios, sugerindo que, neste caso, a quantidade de mediadores químicos liberados dos macrófagos pela Etx seja alta, principalmente de óxido nítrico (NO), causando hipotensäo. Estes resultados mostram que a integridade da regiäo AV3V é importante para os efeitos benéficos da SH. É possível que a produçäo e liberaçäo de NO contribua de modo significativo para os efeitos danosos da Etx. Assim, a descoberta dos mecanismos pelos quais esta molécula atua virá possibilitar a prevençäo e o tratamento mais eficaz do choque produzido por endotoxinas