ALTERED N-METHYL-D-ASPARTATE (NMDA) ACTIVITY IN THE MOUSE SPINAL-CORDFOLLOWING MORPHINE IS MEDIATED BY SIGMA-ACTIVITY

The present study was designed to determine whether the increase in N- methyl-D-aspartate (NMDA) activity in the mouse spinal cord, unmasked by naloxone in morphine-pretreated mice, is mediated by sigma receptor activity. Behavioral responses to intrathecal injections of NMDA were inhibited by pretreatment (2 h) with morphine (10 mg/kg i.p.) except when NMDA was injected together with 0.1 mu g Of naloxone. This excita tory effect of morphine on NMDA-induced behaviors, unmasked in the pre sence of naloxone was prevented but not reversed by haloperidol, a sig ma ligand and dopamine antagonist, but not by an equivalent dose of sp iperone, a dopamine antagonist. Sigma activity also appeared to contri bute to morphine withdrawal jumping in mice as haloperidol inhibited n aloxone-induced jumping while spiperone did not. Together these data i ndicate that naloxone unmasks an action of morphine on NMDA and during acute withdrawal, and these effects are each brought about by mechani sms involving sigma receptor activity.