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Mu-opioid receptors modulate nmda receptor-mediated responses in nucleus accumbens neurons

Academic Article
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Overview

authors

  • Martin, G.
  • Nie, Z. G.
  • Siggins, George

publication date

  • January 1997

journal

  • Journal of Neuroscience  Journal

abstract

  • The nucleus accumbens (NAcc) may play a major role in opiate dependence, and central NMDA receptors are reported to influence opiate tolerance and dependence. Therefore, we investigated the effects of the selective mu-opioid receptor agonist [D-Ala2-N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) on membrane properties of rat NAcc neurons and on events mediated by NMDA and non-NMDA glutamate receptors, using intracellular recording in a brain slice preparation. Most NAcc neurons showed a marked inward rectification (correlated with Cs+- and Ba2+-sensitive inward relaxations) when hyperpolarized, as well as a slowly depolarizing ramp with positive current pulses. Superfusion of DAMGO did not alter membrane potential, input resistance, or the inward relaxations. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) used to block non-NMDA glutamate receptors and bicuculline to block GABAA receptors, EPSPs evoked by local stimulation displayed characteristics of an NMDA component: (1) long duration, (2) voltage sensitivity, and (3) blockade by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (D-APV). DAMGO (0.1-1 muM) significantly decreased both NMDA- and non-NMDA-EPSP amplitudes with reversal of this effect by naloxone and the mu-selective antagonist [Cys2-Tyr3-Orn5-Pen7]-somatostatinamide (CTOP). To assess a postsynaptic action of DAMGO, we superfused slices with tetrodotoxin and evoked inward currents by local application of glutamate agonists. Surprisingly, 0.1-1 microM DAMGO markedly enhanced the NMDA currents (with reversal by CTOP) but reduced the non-NMDA currents. At higher concentrations (5 microM), DAMGO reduced NMDA currents, but this effect was enhanced, not blocked, by CTOP. These results indicate a complex DAMGO modulation of the NMDA component of glutamatergic synaptic transmission in NAcc: mu receptor activation decreases NMDA-EPSP amplitudes presynaptically yet increases NMDA currents postsynaptically. These new data may provide a cellular mechanism for the previously reported role of NMDA receptors in opiate tolerance and dependence.

subject areas

  • Animals
  • Electric Stimulation
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins
  • Excitatory Amino Acid Agonists
  • Kainic Acid
  • Male
  • N-Methylaspartate
  • Neurons
  • Nucleus Accumbens
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid, mu
  • Synapses
  • Synaptic Transmission
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Research

keywords

  • AMPA
  • CTOP
  • DAMGO
  • NMDA-EPSP
  • electrophysiology
  • glutamate
  • intracellular recording
  • kainate
  • naloxone
  • opiate
  • slice preparation
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

PubMed ID

  • 8987732
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Additional Document Info

start page

  • 11

end page

  • 22

volume

  • 17

issue

  • 1

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