N-METHYL-D-ASPARTATE RECEPTORS ARE IMPLICATED IN HYPERRESPONSIVENESS FOLLOWING NALOXONE REVERSAL OF ALFENTANIL IN ISOLATED RAT SPINAL-CORD

In isolated neonatal rat spinal cord, naloxone administered after an o pioid increases a nociceptive-related slow ventral root potential (sVR P) to levels above pre-drug controls. We studied the role of N-methyl- D-aspartate (NMDA) receptors in this phenomenon, which may be related to acute tolerance and to hyperalgesia on antagonist-precipitated with drawal. Naloxone (200 nM) alone produced no significant effect on sVRP area, while naloxone (560 nM) increased area to 121 +/- 17.7% of cont rol (mean +/- SD). Following 200 nM alfentanil, naloxone (200 nM) was associated with a significant rebound in sVRP area to 138 +/- 18.0% of pre-drug control. Hyperresponsiveness developed within 7 min of initi al alfentanil exposure. The non-competitive NMDA antagonist MK-801 (20 nM) had no effect on sVRP area when applied alone; higher concentrati ons produced irreversible depression. MK-801 (20 nM) co-applied with 2 00 nM alfentanil blocked the rebound increase in sVRP area following n aloxone 200 nM and also the increase following naloxone alone (560 nM) . The results suggest that alfentanil induces a rapid NMDA receptor-de pendent change in spinal cord neuronal excitability.