The PKA inhibitor H8 lowers mIPSC frequency and reverses enhanced presynaptic inhibition in β-arrestin2 KO mice. (A) Representative traces before [top two traces, from WT (Left) or from KO (Right) mice] and after 20 min of application of H8 (5 μM, bottom two traces). (B) H8 induced a shift to the right in the cumulative probability histogram of interevent intervals in KO (Right) but not in WT (Left) animals. (Scale bars, 50 pA/2 s.) (C) Dose–response curves for presynaptic inhibition of eIPSCs by morphine (MS) in WT (open symbols), KO (black symbols, P < 0.01 compared with WT for all concentrations >1 μM), and KO in the presence of H8 (gray symbol). Note that the curves fitted with the Hill equation were indistinguishable for WT and KO treated with H8 (n = 5, mean ± SEM). (Right) concentration–response curve for presynaptic inhibition of eIPSC in LC by fentanyl (fenta).