Role of nitric oxide in medullary raphe-evoked inhibition of neuronal activity in the periaqueductal gray matter.

In male urethane-anaesthetized rats, activation of neurons in nucleus raphe obscurus and the caudal tip of nucleus raphe magnus by microinjection of 50-100 nl 0.1 M D,L-homocysteic acid produced a 75.6 +/- 5.2% reduction in the firing rate in 25 neurons in the lateral and dorsolateral sectors of the periaqueductal gray matter which lasted for 102.3 +/- 13.3s (mean +/- S.E.M.). The duration of the inhibition was significantly reduced in a dose-dependent manner by intracerebroventricular injection of the inhibitor of nitric oxide synthase, N(w)-nitro-L-arginine methyl ester (50-500 micrograms) but not by N(w)-nitro-D-arginine methyl ester (500 micrograms). In contrast, the magnitude of the raphe-evoked inhibition, i.e. the maximum depression of firing rate, was not significantly affected by either isomer. The results suggest that nitric oxide plays a role in the regulation of the excitability of neurons in the midbrain aversive system by the medullary raphe. The selective effect of the nitric oxide synthase inhibitor on the duration, but not the magnitude, of the raphe-evoked inhibition suggests that nitric oxide is not involved in initiating the inhibition. Rather, its role appears to be in maintaining the raphe-evoked inhibition once it has been initiated by a non-nitrergic mechanism.