Opiates and opioid peptides may cause excitation of hippocampal pyramidal neurons (HPN) by disinhibition

W. Zieglgaensberger, E. French, G. R. Siggins, F. Bloom

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1 Scopus citations


Microiontophoretically and systemically applied opiates and endorphin peptides depress single unit activity in most areas of the CNS via specific opiate receptors. An apparent exception is the naloxone reversible, non-cholinergic excitatory response observed in a number of rat HPN's by unit recording with iontophoretic application, or by limbic EEG with intraventricular injection. To investigate the nature of this excitatory response, HPN's were tested with multi-barrel iontophoretic pipettes, with double extracellular recording pipettes glued at tip separations of 30-60 μm. When opioid peptides (Met5-enkephalin, D-ala2-met5-enkephalin, β-endorphin) were applied by iontophoresis or by a micro-pressure ejection method most neurons with burst-like firing patterns (probable HPN's) were excited while cells with non-bursting spontaneous activity (probable interneurons) were only inhibited. Low iontophoretic currents of Mg++ (10-30 nA), applied to depress local transmitter release, block opioid excitations and/or reverse them to inhibitions. The GABA-antagonist bicuculline, often excited HPN's and antagonized opioid-induced excitations. Stimulation of contralateral HPC was used to evoke (gabaergic) inhibition of ipsilateral HPN's via basket cells. This inhibition was often specifically antagonized by iontophoretically applied enkephalin. These results suggest that the prolonged excitatory response of hippocampal pyramidal neurons is due to inhibition of adjacent inhibitory interneurons, producing excitation by disinhibition. Thus, while specific opiate receptors may be generally inhibitory including the hippocampus (Fry et al. J.Physiol.Mar 78,21P) the final action of opiates on a region depends upon the local circuitry of the responsive neurons.

Original languageEnglish (US)
Pages (from-to)R34
JournalPflugers Archiv European Journal of Physiology
Issue numberSUPPL.
StatePublished - 1978
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)


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