Chronic morphine exposure blocks opioid effects on both the early and late inhibitory postsynaptic potentials in hippocampal CA1 pyramidal cells.

The mu-opioid agonist, [N-MePhe3,D-Pro4]morphiceptin (PL017), significantly decreased the conductance changes measured during both the early and late inhibitory postsynaptic potentials (IPSP) in CA1 pyramidal cells. Although the conductance change during the early IPSP was much larger than that during the late IPSP, the relative decrease in conductance caused by 1 microM PL017 was similar for both. Chronic morphine treatment of rats prior to hippocampal slice preparation resulted in a loss of PL017 (1 microM) effects on both the early and late IPSPs. These results suggest that opioids have an equal ability to alter both early and late IPSPs in the CA1, that these effects are equally sensitive to chronic morphine, and that these measurements are a sensitive means of determining opioid tolerance in the hippocampus.