Opioid-glutamate interactions in rat locus coeruleus neurons

S. Oleskevich, J. D. Clements, J. T. Williams

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


1. The effect of μ-opioids on the glutamate response was investigated in rat locus coeruleus (LC) neurons by intracellular recording in the brain slice preparation. Glutamate responses were evoked by bath application of selective glutamate agonists, glutamate iontophoresis, and stimulation of excitatory afferents. 2. The μ-opioid agonist D-Ala2-MePhe4-Gly-ol5- enkephalin (DAMGO; 1 μM) potentiated the response to bath application of N- methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid by 91 and 142%, respectively, in slices cut in the horizontal plane. The mechanism of action of this effect was investigated under conditions that limited the DAMGO-induced hyperpolarization and improved the space clamp of the neuron through 1) addition of barium, 2) increase in extracellular potassium concentration, 3) sectioning of the LC in the coronal plane, and 4) addition of carbenoxolone. Each experimental manipulation decreased the DAMGO outward current and reduced the μ-opioid potentiation of the glutamate response. The results suggest that the μ-opioid-mediated potentiation of the glutamate response is dependent on membrane hyperpolarization. 3. Neither forskolin nor the phorbol ester 4b-phorbol 12,13-dibutyrate (PDBu) altered the glutamate-mediated inward currents. The potentiation of the glutamate response by DAMGO was not affected by PDBu. 4. The μ-opioids DAMGO and [met]5 enkephalin (10μM) did not significantly affect the NMDA receptor-mediated depolarization (mean 14%) evoked by local application of glutamate but inhibited the NMDA receptor-mediated synaptic potential (mean 25%). 5. In summary, DAMGO potentiated currents produced by bath-applied glutamate agonists that may result from poor voltage clamp control of the dendrites of LC neurons. Many of the above results could be approximated by a simple passive electrical model of an LC neuron.

Original languageEnglish (US)
Pages (from-to)931-937
Number of pages7
JournalJournal of neurophysiology
Issue number3
StatePublished - 1993

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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