L-NAME prevents EEG and behavioral alterations induced by Morphine and Deltorphin II in the rabbit

The present study investigated the possible role of nitric oxide (NO) in the development of morphineand Deltorphin II-induced elec-troencephalographic (EEG) seizures in rabbits. Central administration of morphine and Deltorphin II (100 μg/icv/toto) produces EEG seizure activity in rabbits, associated with wet-dog shakes, myoclonic twitches and convulsive activity. L-NG-nitro arginine methyl ester (L-NAME) (300 μg/i.c.v./toto) did not induce significant EEG or behavioral changes whereas when injected 15 min before i.c.v. morphine or Deltorphin II (100 μg/icv/toto) dose dependently prevented the EEG ictal episodes, the spiking activity and the synchronized EEG pattern induced by morphine or Deltorphin II. The inhibitory effect of L-NAME on morphine or Deltorphin II seizures was dosedependently reversed by L-arginine (300 μg/icv/toto) but not by D-arginine. Finally, glyceryl trinitrate on its own (300 μg/icv/toto) significantly increased morphine or Deltorphin II seizures in the rabbit and it was also able to reverse the inhibition on morphine or Deltorphin II seizures operated by L-NAME . These results provide evidence that NO may play a significant role in the development of opioids-EEG seizures