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Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of GABAergic inputs.
J Neurophysiol. 2002 Nov; 88(5):2675-83.JN

Abstract

Stimulation of the noradrenergic nucleus locus coeruleus (LC) releases norepinephrine in the spinal cord, which inhibits dorsal horn neurons and produces analgesia. Activation of this descending noradrenergic pathway also contributes to the analgesic action produced by systemic opioids. The delta-opioid receptors are present presynaptically in the LC. However, their functional role in the control of the activity of spinally projecting LC neurons remains uncertain. In this study, we tested the hypothesis that activation of presynaptic delta-opioid receptors excites spinally projecting LC neurons through inhibition of GABA release. Spinally projecting LC neurons were retrogradely labeled by a fluorescent dye, DiI, injected into the spinal dorsal horn of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled LC neurons in brain slices in vitro. Retrogradely labeled LC noradrenergic neurons were demonstrated by dopamine-beta-hydroxylase immunofluorescence. [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE, 1 microM) significantly decreased the frequency of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) of nine DiI-labeled LC neurons from 2.1 +/- 0.5 to 0.7 +/- 0.2 Hz without altering their amplitude and the kinetics. On the other hand, the miniature excitatory postsynaptic currents (EPSC) of nine DiI-labeled LC neurons were not significantly altered by DPDPE. Furthermore, DPDPE significantly inhibited the amplitude of evoked IPSC but not EPSC in eight DiI-labeled LC neurons. Under the current-clamp condition, the firing activity in 9 of 11 DiI-labeled LC neurons was significantly increased by 1 microM DPDPE from 4.6 +/- 0.7 to 6.2 +/- 1.0 Hz. Bicuculline (20 microM) also significantly increased the firing frequency in 13 of 20 neurons from 1.8 +/- 0.5 to 2.8 +/- 0.6 Hz. Additionally, the excitatory effect of DPDPE on LC neurons was diminished in the presence of bicuculline. Collectively, these data strongly suggest that activation of presynaptic delta-opioid receptors by DPDPE excites a population of spinally projecting LC neurons by preferential inhibition of GABA release. Thus presynaptic delta-opioid receptors likely play an important role in the regulation of the excitability of spinally projecting LC neurons and the descending noradrenergic inhibitory system.

Authors+Show Affiliations

Department of Anesthesiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033-0850, USA. hpan@psu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12424303

Citation

Pan, Yu-Zhen, et al. "Activation of Delta-opioid Receptors Excites Spinally Projecting Locus Coeruleus Neurons Through Inhibition of GABAergic Inputs." Journal of Neurophysiology, vol. 88, no. 5, 2002, pp. 2675-83.
Pan YZ, Li DP, Chen SR, et al. Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of GABAergic inputs. J Neurophysiol. 2002;88(5):2675-83.
Pan, Y. Z., Li, D. P., Chen, S. R., & Pan, H. L. (2002). Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of GABAergic inputs. Journal of Neurophysiology, 88(5), 2675-83.
Pan YZ, et al. Activation of Delta-opioid Receptors Excites Spinally Projecting Locus Coeruleus Neurons Through Inhibition of GABAergic Inputs. J Neurophysiol. 2002;88(5):2675-83. PubMed PMID: 12424303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of GABAergic inputs. AU - Pan,Yu-Zhen, AU - Li,De-Pei, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, PY - 2002/11/9/pubmed PY - 2003/1/15/medline PY - 2002/11/9/entrez SP - 2675 EP - 83 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 88 IS - 5 N2 - Stimulation of the noradrenergic nucleus locus coeruleus (LC) releases norepinephrine in the spinal cord, which inhibits dorsal horn neurons and produces analgesia. Activation of this descending noradrenergic pathway also contributes to the analgesic action produced by systemic opioids. The delta-opioid receptors are present presynaptically in the LC. However, their functional role in the control of the activity of spinally projecting LC neurons remains uncertain. In this study, we tested the hypothesis that activation of presynaptic delta-opioid receptors excites spinally projecting LC neurons through inhibition of GABA release. Spinally projecting LC neurons were retrogradely labeled by a fluorescent dye, DiI, injected into the spinal dorsal horn of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled LC neurons in brain slices in vitro. Retrogradely labeled LC noradrenergic neurons were demonstrated by dopamine-beta-hydroxylase immunofluorescence. [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE, 1 microM) significantly decreased the frequency of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) of nine DiI-labeled LC neurons from 2.1 +/- 0.5 to 0.7 +/- 0.2 Hz without altering their amplitude and the kinetics. On the other hand, the miniature excitatory postsynaptic currents (EPSC) of nine DiI-labeled LC neurons were not significantly altered by DPDPE. Furthermore, DPDPE significantly inhibited the amplitude of evoked IPSC but not EPSC in eight DiI-labeled LC neurons. Under the current-clamp condition, the firing activity in 9 of 11 DiI-labeled LC neurons was significantly increased by 1 microM DPDPE from 4.6 +/- 0.7 to 6.2 +/- 1.0 Hz. Bicuculline (20 microM) also significantly increased the firing frequency in 13 of 20 neurons from 1.8 +/- 0.5 to 2.8 +/- 0.6 Hz. Additionally, the excitatory effect of DPDPE on LC neurons was diminished in the presence of bicuculline. Collectively, these data strongly suggest that activation of presynaptic delta-opioid receptors by DPDPE excites a population of spinally projecting LC neurons by preferential inhibition of GABA release. Thus presynaptic delta-opioid receptors likely play an important role in the regulation of the excitability of spinally projecting LC neurons and the descending noradrenergic inhibitory system. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/12424303/Activation_of_delta_opioid_receptors_excites_spinally_projecting_locus_coeruleus_neurons_through_inhibition_of_GABAergic_inputs_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00298.2002?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -