Differential profiles of nitric oxide and norepinephrine releases in the paraventricular nucleus region in response to mild footshock in rats

The purpose of this study was to determine whether the application of mild intermittent footshock stress can cause changes in the nitric oxide (NO) an d norepinephrine (NE) releases in the hypothalamic paraventricular nucleus (PVN) region and medial prefrontal cortex (mPFC). Extracellular levels of N O metabolites and NE in the PVN region and mPFC were determined using an in vivo brain microdialysis technique in conscious rats. In the PVN region, w e demonstrated that perfusion of N-methyl-D-aspartate through a microdialys is probe resulted in a dose-dependent increase in NO metabolite levels, whe reas intraperitoneal administration of N-G-nitro-L-arginine methyl ester pr oduced a dose-dependent reduction in the levels of NO metabolites. The leve ls of NO metabolites in the PVN region increased after intraperitoneal admi nistration of interleukin-1 beta in a dose-dependent manner, as we previous ly reported. This increase in NO metabolite levels was abolished 60 min aft er systemic administration of NG-nitro-L-arginine methyl ester compared to the vehicle-treated control group. Twenty minutes of intermittent footshock induced NE release but did not induce NO release in the PVN region. On the contrary, in the mPFC, 20 min of intermittent footshock induced both NO an d NE releases. The present results reveal different patterns and time cours es in NO and NE releases between the PVN region and the mPFC in response to mild intermittent footshock stress. These findings are likely to have help ful suggestions for our understanding of the hypothalamic-pituitary-adrenal axis and the limbic forebrain system response to different kinds of stress . (C) 2000 Elsevier Science B.V. All rights reserved.