NO synthase inhibitors reduce opioid desensitization in rat locus coeruleus neurons in vitro.

The aim of this study was to examine by electrophysiological techniques whether nitric oxide (NO) is involved in the development of desensitization to the opioid agonist Met5-enkephalin (ME) in locus coeruleus neurons from rat brain slices. Bath perfusion with ME (0.05-1.6 microM) caused a concentration-dependent reduction in the firing rate of locus coeruleus cells, whereas perfusion with a high concentration of ME (10 microM) desensitized the inhibitory effect of subsequent ME (0.8 microM) applications. However, in slices perfused with the NO synthase inhibitors 7-NI (100 microM), L-NAME (100 microM) or L-NA (100 microM) the ME (10 microM)-induced opioid desensitization was strongly attenuated. The effect of L-NAME was prevented by administration of L-arginine (100 microM). These results suggest that nitric oxide may contribute to opioid desensitization in locus coeruleus neurons.