Figure 6.

Combinations of MOR and DOR agonists produce synaptic synergism. A, Dose-dependent inhibition of IPSCs by a mixture of DAMGO and deltorphin at a fixed ratio of 9:1 in neurons from morphine-treated rats. N=5–7 cells for each data point. B, Normalized data of dose-dependent IPSC inhibition by DAMGO, deltorphin and the mixture (experimental), fitted by a regression line, and a calculated theoretical line of additivity in neurons from the morphine group. N=5–16 cells for each data point. C, Isobolograph of EC₅₀ values and their 95% confidence limits (vertical and horizontal bars) for theoretical additivity and for experimentally derived data (squares) with a DAMGO:deltorphin mixture of 9:1 and 1:1 ratios. For comparison, theoretical EC₅₀ values for simple additivity at both 9:1 and 1:1 mixture ratios are also depicted as cross bars (95% confidence limits) without symbols on the theoretical line. D, Dose-response curves for IPSC inhibition by DAMGO and by the mixture (9:1) plus AACOCF3 (1 μM). N=5–12 cells for each data point. E, F, Similar dose-dependent data of regression lines and a theoretical line (E), and isobolograph of EC₅₀ values (F) except that the experimental data of the mixture (9:1) were obtained in the presence of AACOCF3 (1 μM). N=5–16 cells for each data point. G, Effects of lower doses of the AC inhibitor SQ22536 on DAMGO inhibition of IPSCs in neurons of the morphine group. H, Antagonizing effect of 1 μM SQ22536 on the IPSC inhibition induced by the mixture at 10 nM (n=10) and 30 nM (n=7). N=5–16 for other data points. * p<0.05, ** p<0.01. Scale bars are 100 pA and 50 ms.