We first assessed the effect of dynorphin (dynorphin A [1–17]), an endogenous kappa receptor agonist, on GABAergic transmission. Superfusion of 1 μM dynorphin consistently decreased Inhibitory PostSynaptic Potentials (IPSPs) in 80% of the neurons exposed to the peptide (12 of 15.) The depressant effect of dynorphin developed immediately after the start of application and reached a maximum effect after 9 minutes of superfusion (Fig. 1A,B). Upon washout of the peptide, IPSP amplitude recovered to control level within 20 minutes (4 of 4 experiments). On average (mean of 4 points after steady level reached and just before change of condition), IPSP amplitudes were significantly decreased to 79 ± 4% of control (n = 12, t = 6.568). The dynorphin decrease of IPSP amplitude persisted upon extended application of the peptide for 25 minutes (n = 2 at 1 μM; n = 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
