Met- and leu-enkephalins inhibit rat cortical neurons intracellularly recorded in vivo while morphine excites them: evidence for naloxone-sensitive and naloxone-insensitive effects

The action of enkephalin-analogues (D-ala2-D-leu5-enkephalin and D-ala2-D-met-enkephalin) and morphine, iontophoretically applied, was tested on rat cortical neurons intracellularly recorded "in vivo". Inhibition of cellular excitability of 60% of the tested cells followed the iontophoretic administration of opioid peptides. 50% of the inhibited cells were also hyperpolarized. The amplitude of membrane hyperpolarization was related to the value of the membrane potential. In 13 out of the 30 inhibited cells the change in membrane input resistance was measured; the input resistance was decreased by 30%. In 8 cells, hyperpolarized by the opioid peptides, the depolarizing postsynaptic potentials, evoked by cortical stimulation, were also reduced in amplitude. Naloxone, iontophoretically applied, reversed and/or prevented the peptide responses. On the same neurons, morphine induced a bursting pattern of spiking activity and increased the membrane input resistance: this action was naloxone-insensitive. The reported results suggest that opioid peptides and morphine activate, respectively, naloxone-sensitive and naloxone-insensitive mechanisms on the same cortical neurons, leading to different and, in some respect, opposite effects on the neuronal activity.