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Journal of Neuroscience, Vol 14, 134-139, Copyright © 1994 by Society for Neuroscience
Extracellular cGMP in the hippocampus of freely moving rats as an index of nitric oxide (NO) synthase activity
F Vallebuona and M Raiteri
Institute of Pharmacology and Pharmacognosy, University of Genova, Italy.
The nitric oxide (NO) synthase/cGMP pathway has been studied in vivo in the
adult rat hippocampus by monitoring the levels of extracellular cGMP during
microdialysis in conscious unrestrained animals. The basal cGMP efflux was
concentration-dependently reduced upon local infusion of the NO synthase
inhibitor NG-nitro-L-arginine (NARG; 10 microM to 1 mM). The NO donors
hydroxylamine and S-nitroso-N-penicillamine, perfused through the dialysis
probe at 1 mM, increased by about 200% the extracellular levels of cGMP.
The glutamate receptor agonist NMDA (125-500 microM) produced
concentration-dependent cGMP responses that were abolished by the selective
receptor antagonist D-2-amino-5- phosphonovaleric acid or by NARG. Local
perfusion of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
(IBMX; 1 mM) produced a steady eightfold increase of extracellular cGMP
levels. The effect of IBMX was highly sensitive to NARG. The inhibition by
NARG of the IBMX-induced cGMP response was reversed when the NO synthase
substrate L-arginine was administered. It is concluded that cGMP collected
during in vivo microdialysis reflects NO synthase activity in the rat
hippocampus. The technique may be utilized to investigate the
pathophysiology and the pharmacology of the NO/cGMP pathway in the
hippocampus of living animals.
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