Effect of Activation and Blockade of Nitrergic Neurotransmission on Serotonin System Activity of the Rat Medial Prefrontal Cortex

Nitric oxide (NO) and serotonin play an important role in the functioning of the medial prefrontal cortex, but their interaction has been poorly explored. The aim of this work was to study the effects of local nitrergic signals on the activity of the serotonin system in this cortical area. In male Sprague-Dawley rats, using in vivo microdialysis, we showed that the infusion of diethylamine nonoate (0.1 mM, 0.5 mM, 1 mM), an NO donor, into the medial prefrontal cortex led to an increase in extracellular serotonin levels, which correlated with the drug concentration during the first 15 min of infusion. Diethylamine nonoate, at a concentration of 2.5 mM, reduced extracellular seritonin levels. Infusion of N-nitro-L-arginine (0.5 mM), an NO synthase inhibitor, into the medial prefrontal cortex decreased the basal extracellular serotonin level in this area, as well as delayed and attenuated a rise in the serotonin level caused by the local administration of fluoxetine (10 mu M), a selective serotonin reuptake inhibitor. These findings indicate that in the medial prefrontal cortex, in a quiet waking state, tonic endogenous nitrergic signals, as well as their moderate pharmacological enhancement by NO donor administration, activates the serotonin system in this area by increasing the extracellular serotonin pool, while a stronger nitrergic stimulation acts in the opposite way.