NITRIC-OXIDE SYNTHESIS INHIBITION ATTENUATES BEHAVIORAL ACTIONS OF NEUROPEPTIDE FF

Neuropeptide FF (NPFF) has certain antiopiate actions and may play a r ole in opiate tolerance and dependence. Third ventricle injection of 1 0 mu g NPFF induces a quasimorphine abstinence syndrome in opiate-naiv e rats. Nitric oxide synthesis may also contribute to opiate tolerance and dependence. The present study tests the hypothesis that NPFF acts through stimulation of nitric oxide synthase (NOS). Third ventricular injection of 10 mu g NPFF precipitated an average of 46 abstinence-li ke signs during a 20-min observation. Pretreatment (30 min earlier) wi th 7.5 or 15 mg/kg SC of the NOS inhibitor nitro-L-arginine (L-NNA) re sulted in a significant and dose-dependent alleviation of NPFF-induced abstinence-like signs. The anti-NPFF activity of 15 mg/kg L-NNA was b locked by 750 mg/kg L-arginine, but not by the same amount of D-argini ne, indicating that L-NNA attenuates NPFF activity through a stereospe cific inhibition of NOS.