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Dissociation of mu and delta opioid receptor-mediated reductions in evoked and spontaneous synaptic inhibition in the rat hippocampus in vitro.
Brain Res. 1992 Oct 16; 593(2):226-38.BR

Abstract

Modulation of gamma-aminobutyric acid (GABA)-mediated inhibition, and glutamate-mediated excitation by highly selective mu and delta opioid agonists was studied using intracellular recordings of CA1 pyramidal neuron synaptic responses in superfused hippocampal slices. Equimolar concentrations of the selective mu agonist, [Tyr-(D-Ala)-Gly-(N-Me-Phe)-Gly-ol]-enkephalin (DAGO), or the delta selective agonist, [D-Pen2,D-Pen5]-enkephalin (DPDPE), reversibly increased the amplitudes of excitatory post-synaptic potentials (EPSPs), evoked by Schaffer collateral/commissural stimulation, without altering the input resistance or resting membrane potential of these CA1 pyramidal neurons. The increased EPSP amplitudes resulting from superfusion with the enkephalin analogs were qualitatively similar to those caused by the GABAA receptor antagonist, bicuculline methiodide (BMI). Specific stimulation/recording protocols and micro-lesions of the slices were used to evoke relatively pure forms of recurrent and feed-forward GABA-mediated inhibitory post-synaptic potentials (IPSPs). The mu opioid agonist DAGO reduced both recurrent and feed-forward IPSPs, while the delta agonist DPDPE had no effect upon these responses. To test the hypothesis that the enhancement of pyramidal neuron EPSPs by delta (and mu) opioids was due to the reduction of an inhibitory potential that was coincident with the EPSP, DPDPE or the mu agonist, DAGO, were applied while recording monosynaptic IPSPs following the elimination of EPSPs by the glutamate receptor antagonists, D,L-2-amino-5-phosphonovalerate (APV) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). The mu agonist, DAGO, reversibly reduced these pharmacologically isolated IPSPs, while the delta agonist, DPDPE, had no effect upon these responses. Despite the fact that the delta agonist, DPDPE, had no effect on recurrent, feed-forward or monosynaptic evoked IPSPs, this enkephalin did reversibly reduce the frequency of spontaneously occurring IPSPs, measured using whole-cell recordings with pipettes containing 65 mM KCl. The mu agonist, DAGO, and the GABAA antagonist, BMI, similarly reduced spontaneous IPSP rates. We conclude from these data that mu and delta opioid receptor activation increases EPSPs via the reduction of a form of GABAergic inhibition that is difficult to characterize, and which may be distinct from conventional feed-forward and recurrent inhibition. Furthermore, delta opioids seem to reduce this form of GABAergic inhibition selectively, while mu opioids reduced this inhibition, and conventional feed-forward and recurrent IPSPs as well.

Authors+Show Affiliations

Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1360320

Citation

Lupica, C R., et al. "Dissociation of Mu and Delta Opioid Receptor-mediated Reductions in Evoked and Spontaneous Synaptic Inhibition in the Rat Hippocampus in Vitro." Brain Research, vol. 593, no. 2, 1992, pp. 226-38.
Lupica CR, Proctor WR, Dunwiddie TV. Dissociation of mu and delta opioid receptor-mediated reductions in evoked and spontaneous synaptic inhibition in the rat hippocampus in vitro. Brain Res. 1992;593(2):226-38.
Lupica, C. R., Proctor, W. R., & Dunwiddie, T. V. (1992). Dissociation of mu and delta opioid receptor-mediated reductions in evoked and spontaneous synaptic inhibition in the rat hippocampus in vitro. Brain Research, 593(2), 226-38.
Lupica CR, Proctor WR, Dunwiddie TV. Dissociation of Mu and Delta Opioid Receptor-mediated Reductions in Evoked and Spontaneous Synaptic Inhibition in the Rat Hippocampus in Vitro. Brain Res. 1992 Oct 16;593(2):226-38. PubMed PMID: 1360320.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissociation of mu and delta opioid receptor-mediated reductions in evoked and spontaneous synaptic inhibition in the rat hippocampus in vitro. AU - Lupica,C R, AU - Proctor,W R, AU - Dunwiddie,T V, PY - 1992/10/16/pubmed PY - 1992/10/16/medline PY - 1992/10/16/entrez SP - 226 EP - 38 JF - Brain research JO - Brain Res VL - 593 IS - 2 N2 - Modulation of gamma-aminobutyric acid (GABA)-mediated inhibition, and glutamate-mediated excitation by highly selective mu and delta opioid agonists was studied using intracellular recordings of CA1 pyramidal neuron synaptic responses in superfused hippocampal slices. Equimolar concentrations of the selective mu agonist, [Tyr-(D-Ala)-Gly-(N-Me-Phe)-Gly-ol]-enkephalin (DAGO), or the delta selective agonist, [D-Pen2,D-Pen5]-enkephalin (DPDPE), reversibly increased the amplitudes of excitatory post-synaptic potentials (EPSPs), evoked by Schaffer collateral/commissural stimulation, without altering the input resistance or resting membrane potential of these CA1 pyramidal neurons. The increased EPSP amplitudes resulting from superfusion with the enkephalin analogs were qualitatively similar to those caused by the GABAA receptor antagonist, bicuculline methiodide (BMI). Specific stimulation/recording protocols and micro-lesions of the slices were used to evoke relatively pure forms of recurrent and feed-forward GABA-mediated inhibitory post-synaptic potentials (IPSPs). The mu opioid agonist DAGO reduced both recurrent and feed-forward IPSPs, while the delta agonist DPDPE had no effect upon these responses. To test the hypothesis that the enhancement of pyramidal neuron EPSPs by delta (and mu) opioids was due to the reduction of an inhibitory potential that was coincident with the EPSP, DPDPE or the mu agonist, DAGO, were applied while recording monosynaptic IPSPs following the elimination of EPSPs by the glutamate receptor antagonists, D,L-2-amino-5-phosphonovalerate (APV) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). The mu agonist, DAGO, reversibly reduced these pharmacologically isolated IPSPs, while the delta agonist, DPDPE, had no effect upon these responses. Despite the fact that the delta agonist, DPDPE, had no effect on recurrent, feed-forward or monosynaptic evoked IPSPs, this enkephalin did reversibly reduce the frequency of spontaneously occurring IPSPs, measured using whole-cell recordings with pipettes containing 65 mM KCl. The mu agonist, DAGO, and the GABAA antagonist, BMI, similarly reduced spontaneous IPSP rates. We conclude from these data that mu and delta opioid receptor activation increases EPSPs via the reduction of a form of GABAergic inhibition that is difficult to characterize, and which may be distinct from conventional feed-forward and recurrent inhibition. Furthermore, delta opioids seem to reduce this form of GABAergic inhibition selectively, while mu opioids reduced this inhibition, and conventional feed-forward and recurrent IPSPs as well. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/1360320/Dissociation_of_mu_and_delta_opioid_receptor_mediated_reductions_in_evoked_and_spontaneous_synaptic_inhibition_in_the_rat_hippocampus_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0006-8993(92)91312-3 DB - PRIME DP - Unbound Medicine ER -