NONOPIOID ACTIONS OF THE K-OPIOID RECEPTOR AGONISTS, U-50488H AND U-69593, ON ELECTROPHYSIOLOGIC PROPERTIES OF HIPPOCAMPAL CA3 NEURONS INVITRO

  • 1 November 1990
    • journal article
    • research article
    • Vol. 255  (2) , 900-905
Abstract
The actions of the nonpeptide .kappa.-opioid receptor agonists, U 50488H (1-100 .mu.M) and U 69593 (50-200 .mu.M), on guinea pig hippocampal CA3 neurons were investigated in vitro by means of intra- and extracellular recording techniques. The compounds reduced the efficacy of synaptic transmission at the mossy fiber-CA3 synapse, and simultaneously, enhanced the neuronal direct excitability. Intracellular recordings from CA3 neurons suggested two components underlying the drugs'' excitatory actions: 1) Due to an apparent decrease in membrane leak conductance, the compounds enhanced the neuronal input resistance in a dose-dependent fashion. 2) The fast after-hyperpolarization following spontaneous or evoked action potentials was found to be substantially impaired in the presence of the drugs. In addition, extra- and intracellular recordings provided evidence that, by reducing the fast sodium conductance, both compounds exerted a local anesthetic action. The effects of U 50488H were antagonized neither by naloxone (2-50 .mu.M) nor by the .kappa.-opioid receptor antagonist, nor-binaltorphimine (10-20 .mu.M), indicating that the drug-induced effects represent unspecific actions not linked to activation of opioid receptors.

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