Figure 2.

Increased EPSC frequencies in slices from morphine-tolerant rats are attributable to NMDA receptor-mediated currents. A, The NMDA receptor antagonist APV (25 μm) inhibits the frequency of sEPSCs recorded in slices from morphine-treated rats (Tolerant), but not opiate-naive rats (Naive), such that after APV there is no longer a significant difference in sEPSC frequency between the two groups of slices. The kainate/AMPA glutamate receptor antagonist CNQX (10 μm) virtually eliminated all sEPSCs in lamina I cells from morphine-treated rats, mirroring our previous data in opiate-naive slices and demonstrating the absence of postsynaptic NMDAR-mediated currents in our recordings. B, Elevated mEPSC frequencies in slice recordings of neurons (n) from morphine-treated rats (Tolerant) also were diminished by APV to levels of mEPSC frequencies observed in opiate-naive slices (Naive) by APV, even when the NMDA antagonist MK-801 was added to the intracellular pipette solution to block postsynaptic NMDA receptors. Data in both A and B represent repeated measure experiments in which APV or CNQX was added to the perfusate for 10 min. Statistical analysis was performed by using either between-group or repeated measures ANOVA as appropriate, although predrug data (Naive or Tolerant) were collapsed across APV, CNQX, or no drug treatments for presentation purposes. Graphed values are the means ± SEM; *p < 0.05 signifies a significant difference from opiate-naive slices.