Selective opposite modulation of dentate granule cells excitability by mu and kappa opioids in rat hippocampal slices

The effects of opioids having affinity for kappa (U50,488H and U54,494A) and mu receptors (DAMGO and methadone) were tested on the excitability of the dentate and CA1 neurons in rat hippocampal slices. Slice perfusion with 25 mu M U50,488H or with 12 mu M U54,494A produced within 60 min a significant (P < 0.05) decrease in the amplitude of the primary dentate population spike (PS). A similar decrease occurred on the CA1 PS amplitude only at concentrations higher than 100 mu M of U50,488H or 50 mu M of U54,494A. Slice perfusion with 0.5 mu M DAMGO, or 100 mu M methadone: produced an increase in the amplitude of the primary dentate and CA1 PS and the appearance of secondary PSs. Slice perfusion with 12 mu M U50,488H or with 25 mu M of methadone significantly (P < 0.05) decreased or increased, respectively, the rate of appearance of the dentate posttetanic potentiation (PTP) and long-term potentiation (LTP) after a 100 Hz tetanic stimulation of the perforant path. The same concentration of U50,488H or methadone did not affect the rate of appearance of the CA1 PTP and LTP after a 100 Hz tetanic stimulation of the Schaffer collaterals. The data, providing evidence for a selective opposite modulation by mu and kappa opioids on the basal and stimulated dentate neuronal excitability, indicate the dentate area as a target within the hippocampus for an opposite influence between mu and kappa opioids on neuronal excitability.