Back to Search
Start Over
Activation of mu-opioid receptors inhibits synaptic inputs to spinally projecting rostral ventromedial medulla neurons.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2004 May; Vol. 309 (2), pp. 476-83. Date of Electronic Publication: 2004 Jan 14. - Publication Year :
- 2004
-
Abstract
- The rostral ventromedial medulla (RVM) is a major locus for the descending control of nociception and opioid analgesia. However, it is not clear how opioids affect synaptic inputs to RVM neurons. In this study, we determined the effect of mu-opioid receptor activation on excitatory and inhibitory synaptic transmission in spinally projecting RVM neurons. RVM neurons were retrogradely labeled with a fluorescent tracer injected into the dorsal horn of the spinal cord in rats. Whole-cell voltage-clamp recordings were performed on labeled RVM neurons in brain slices in vitro. The mu-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO, 1 microM) significantly decreased the amplitude of evoked excitatory postsynaptic currents (EPSCs) in 52% (9 of 17) of labeled cells. DAMGO also significantly reduced the amplitude of evoked inhibitory postsynaptic currents (IPSCs) in 69% (11 of 16) of cells examined. Furthermore, DAMGO significantly decreased the frequency of miniature EPSCs in 55% (15 of 27) of cells and significantly decreased the frequency of miniature IPSCs in all 12 cells studied. Although most EPSCs and IPSCs were mediated by glutamate and GABA, the nicotinic and glycine receptor antagonists attenuated EPSCs and IPSCs, respectively, in some labeled RVM neurons. Immunocytochemical labeling revealed that only 35% of recorded RVM neurons were tryptophan hydroxylase-positive, and 15% cells had GABA immunoreactivity. Thus, this study provides important functional evidence that activation of mu-opioid receptors decreases the release of both excitatory and inhibitory neurotransmitters onto most spinally projecting RVM neurons.
- Subjects :
- Analgesics, Opioid pharmacology
Animals
Female
Male
Neurons enzymology
Neurons metabolism
Rats
Rats, Sprague-Dawley
Receptors, Opioid, mu agonists
Spinal Cord drug effects
Spinal Cord physiology
Tryptophan Hydroxylase immunology
Tryptophan Hydroxylase metabolism
gamma-Aminobutyric Acid immunology
gamma-Aminobutyric Acid metabolism
gamma-Aminobutyric Acid pharmacology
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology
Medulla Oblongata cytology
Neurons drug effects
Receptors, Opioid, mu metabolism
Synaptic Transmission drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 309
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 14724227
- Full Text :
- https://doi.org/10.1124/jpet.103.064808