NO synthase inhibitors attenuate locus coeruleus catecholamine metabolism and behavior induced by morphine withdrawal

The effects of nitric oxide synthase (NOS) inhibitors were examined simultaneously on the behavior and on the catecholaminergic metabolism in the locus coeruleus (LC) during morphine withdrawal using microdialysis in freely moving rats. Morphine withdrawal was precipitated by naltrexone administration to morphine-treated rats. Acute pretreatment of rats with NOmicron-nitro-L-arginine-p-nitroanilide (L-NAPNA) or 7-nitroindazole (7-NI) before naltrexone challenge attenuated the behavioral expression of morphine withdrawal and strongly reduced the withdrawal-induced increase in 3,4-dihydroxyphenylacetic acid (DOPAC) in the LC. The two NOS inhibitors also decreased DOPAC in absence of naltrexone challenge. These results suggest a role for NO in the expression of morphine withdrawal syndrome that may be mediated, at least in part, by LC noradrenergic neurons.