CORRELATION BETWEEN BRAIN NITRIC-OXIDE SYNTHASE ACTIVITY AND OPIATE WITHDRAWAL

The opiate withdrawal induced by administration of naloxone to morphin e-dependent mice correlates with an increment of calcium- dependent ni tric oxide synthase (NOS) activity in the cerebellum. L-NAME, an irrev ersible competitive inhibitor of NOS (0.5, 5, 25, 50 mg/kg) injected s c. 45 min. prior to naloxone significantly reduced the number of escap e jumps and other motor symptoms of abstinence. In addition, L-NAME al so decreased NOS activity in cerebellum. L-arginine, but not D-arginin e, when coadministered with L-NAME, prevented both the inhibition of N OS activity and the reduction of withdrawal symptoms induced by L-NAME in morphine-withdrawn animals. These results demonstrate a hyperactiv ity of the L-arginine: NO pathway in opiate withdrawal and suggests th e possibility of a therapeutic use of NOS inhibitors in this state.