INCREASED N-METHYL-D-ASPARTATE (NMDA) ACTIVITY IN THE MOUSE SPINAL-CORD FOLLOWING MORPHINE DOES NOT MEDIATE OPIOID WITHDRAWAL

N-Methyl-D-aspartate (NMDA) receptors have been proposed to play a rol e in opioid tolerance and dependence. The present study was designed t o determine whether the increased NMDA activity in the spinal cord, un masked by naloxone in morphine-pretreated mice, reflects activity lead ing to opioid withdrawal. Behavioral responses to intrathecal injectio ns of NMDA were inhibited by pretreatment (2 h) with morphine (10 mg/k g i.p,), but enhanced following morphine when naloxone was injected to gether with NMDA. Although injected at doses that inhibited NMDA activ ity, the excitatory effects of morphine on NMDA-induced behaviors were prevented by dizocilpine (MK-801), a phencyclidine (PCP) ligand, but not by 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1 phosphonic acid (CPP ), a competitive NMDA antagonist. MK-801 also inhibited naloxone-induc ed withdrawal jumping, however, just as CPP failed to affect morphine- induced changes in NMDA-induced behaviors, CPP also failed to inhibit withdrawal jumping. Together these data indicate that withdrawal from acute opioid dependence correlates with, but is not mediated by enhanc ed NMDA activity.