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Activation of delta-opioid receptors excites spinally projecting locus coeruleus neurons through inhibition of GABAergic inputs.
- Source :
-
Journal of neurophysiology [J Neurophysiol] 2002 Nov; Vol. 88 (5), pp. 2675-83. - Publication Year :
- 2002
-
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.
- Subjects :
- 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology
Analgesics, Opioid pharmacology
Animals
Bicuculline pharmacology
Dopamine beta-Hydroxylase metabolism
Electrophysiology
Enkephalin, D-Penicillamine (2,5)- pharmacology
Excitatory Postsynaptic Potentials physiology
GABA Antagonists pharmacology
Immunohistochemistry
Locus Coeruleus cytology
Naltrexone pharmacology
Narcotic Antagonists pharmacology
Neural Pathways cytology
Neural Pathways physiology
Presynaptic Terminals drug effects
Presynaptic Terminals physiology
Rats
Rats, Sprague-Dawley
Spinal Cord cytology
Locus Coeruleus physiology
Naltrexone analogs & derivatives
Neurons physiology
Receptors, Opioid, delta agonists
Spinal Cord physiology
gamma-Aminobutyric Acid physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3077
- Volume :
- 88
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of neurophysiology
- Publication Type :
- Academic Journal
- Accession number :
- 12424303
- Full Text :
- https://doi.org/10.1152/jn.00298.2002