2 at 2 μM), demonstrating a lack of short term desensitization of KOR in our preparation. Another neuron did not respond and another 2 showed a slight IPSP increase (10–15 %) upon exposure to dynorphin. We used the selective KOR antagonist nor-binaltorphimine (norBNI) (Portoghese et al., 1987) to confirm that dynorphin decreased IPSPs by activating KOR. In the presence of 0.2 μM norBNI, dynorphin did not affect IPSPs which remained at 98 ± 4% of pre-dynorphin level (n = 4; Fig 1C). The dynorphin-elicited decrease of inhibitory transmission was concentration-dependent. We observed no effect of 0.1 μM dynorphin (101 ± 4% of control, n = 3), whereas IPSPs were decreased to 96 ± 5% of control with 0.2 μM dynorphin (n = 3), to 91 ± 5% with 0.5 μM (n = 4) and 77 ± 5% with 2 μM (n = 6). We used a sigmoidal (logistic) fit to analyze the concentration-response relationship (Fig. 2A). The apparent EC50 for dynorphin to decrease IPSPs was 0.5 μM. We conclude that the endogenous peptide dynorphin concentration-dependently decreases inhibitory transmission in CeA by activating KOR.
