In vivo NO/cGMP signalling in the hippocampus

In the hippocampus of freely-moving rats, basal extracellular levels of cGM P are inhibited by L-NARG or ODQ whereas they are increased by NO donors or phosphodiesterase inhibitors. Activation of NMDA receptors also augments c GMP dialysate levels in a MK-801 and L-NARG sensitive manner, an effect dra matically diminished during ageing. Experiments with AMPA, AMPA receptor an tagonists and cyclothiazide revealed complex relationships with GABAergic c ircuits that potently control the NO/cGMP pathway. Furthermore, the activit y of this neurochemical cascade is also modulated by hippocampal nicotinic receptors via enhancement of endogenous glutamate release and stimulation o f NMDA receptors. From a behavioural point of view, increased hippocampal e xcitation leads to the appearance of epileptic-like manifestations that, ho wever, seem unrelated to the increase of NO/cGMP formation.