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Activation of mu-opioid receptors excites a population of locus coeruleus-spinal neurons through presynaptic disinhibition.
- Source :
-
Brain research [Brain Res] 2004 Jan 30; Vol. 997 (1), pp. 67-78. - Publication Year :
- 2004
-
Abstract
- The nucleus locus coeruleus (LC) plays an important role in analgesia produced by opioids and by modulation of the descending noradrenergic pathway. The functional role of micro-opioid receptors (muOR) in regulation of the excitability of spinally projecting LC neurons has not been investigated. In the present study, we tested the hypothesis that activation of presynaptic mu-opioid receptors excites a population of spinally projecting LC neurons through attenuation of gamma-aminobutyric acid (GABA)-ergic synaptic inputs. Spinally projecting LC neurons were retrogradely labeled by a fluorescent dye injected into the spinal dorsal horn of rats. Whole-cell current- and voltage-clamp recordings were performed on labeled LC neurons in brain slices. All labeled LC noradrenergic neurons were demonstrated by dopamine-beta-hydroxylase (DbetaH) immunofluorescence. In 37 labeled LC neurons, (D-Ala(2),N-Me-Phe(4),Gly-ol(5))-enkephalin (DAMGO) significantly increased the discharge activity of 17 (45.9%) neurons, but significantly inhibited the firing activity of another 15 (40.5%) cells. The excitatory effect of DAMGO on seven labeled LC neurons was diminished in the presence of bicuculline. DAMGO significantly decreased the frequency of GABA-mediated miniature inhibitory postsynaptic currents (mIPSCs) in all nine labeled LC neurons. However, DAMGO had no effect on glutamate-mediated miniature excitatory postsynaptic currents (mEPSCs) in 12 of 15 neurons. Furthermore, DAMGO significantly inhibited the peak amplitude of evoked inhibitory postsynaptic currents (eIPSCs) in all 11 labeled neurons, but had no significant effect on the evoked excitatory postsynaptic currents (eEPSCs) in 10 of these 11 neurons. Thus, data from this study suggest that activation of micro-opioid receptors excites a population of spinally projecting LC neurons by preferential inhibition of GABAergic synaptic inputs. These findings provide important new information about the descending noradrenergic modulation and analgesic mechanisms of opioids.
- Subjects :
- 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology
Analgesics, Opioid pharmacology
Anesthetics, Local pharmacology
Animals
Bicuculline pharmacology
Carbocyanines metabolism
Dopamine beta-Hydroxylase metabolism
Drug Interactions
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology
Excitatory Amino Acid Antagonists pharmacology
Excitatory Postsynaptic Potentials drug effects
Excitatory Postsynaptic Potentials physiology
GABA Antagonists pharmacology
Immunohistochemistry
In Vitro Techniques
Locus Coeruleus drug effects
Locus Coeruleus metabolism
Membrane Potentials drug effects
Neural Inhibition drug effects
Neurons drug effects
Patch-Clamp Techniques methods
Peptides pharmacology
Presynaptic Terminals drug effects
Rats
Rats, Sprague-Dawley
Receptors, Opioid, mu antagonists & inhibitors
Spinal Cord drug effects
Tetrodotoxin pharmacology
gamma-Aminobutyric Acid pharmacology
Locus Coeruleus cytology
Neurons metabolism
Presynaptic Terminals physiology
Receptors, Opioid, mu metabolism
Spinal Cord metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 997
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 14715151
- Full Text :
- https://doi.org/10.1016/j.brainres.2003.10.050