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Effect of the {mu} opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2005 Feb; Vol. 312 (2), pp. 441-8. Date of Electronic Publication: 2004 Sep 23. - Publication Year :
- 2005
-
Abstract
- Opioids are potent analgesics, but the sites of their action and cellular mechanisms are not fully understood. The central nucleus of the amygdala (CeA) is important for opioid analgesia through the projection to the periaquaductal gray (PAG). In this study, we examined the effects of mu opioid receptor stimulation on inhibitory and excitatory synaptic inputs to PAG-projecting CeA neurons retrogradely labeled with a fluorescent tracer injected into the ventrolateral PAG of rats. Whole-cell voltage-clamp recordings were performed on labeled CeA neurons in brain slices. The specific mu opioid receptor agonist, [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO, 1 microM), significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) without altering the amplitude and decay constant of mIPSCs in 47.6% (10 of 21) of cells tested. DAMGO also significantly decreased the peak amplitude of evoked IPSCs in 69% (9 of 13) of cells examined. However, DAMGO did not significantly alter the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of evoked EPSCs in 69% (9 of 13) and 83% (10 of 12) of labeled cells, respectively. The IPSCs were blocked by the GABA(A) receptor antagonist bicuculline, whereas the EPSCs were largely abolished by the non-N-methyl-d-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. The immunoreactivity of mu opioid receptors was colocalized with synaptophysin, a presynaptic marker, in close appositions to labeled CeA neurons. These results suggest that activation of mu opioid receptors on presynaptic terminals primarily attenuates GABAergic synaptic inputs to PAG-projecting neurons in the CeA.
- Subjects :
- Amygdala drug effects
Analgesics, Opioid pharmacology
Animals
Bicuculline pharmacology
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology
Excitatory Postsynaptic Potentials drug effects
GABA Antagonists pharmacology
Immunohistochemistry
In Vitro Techniques
Male
Membrane Potentials drug effects
Neural Pathways cytology
Neural Pathways drug effects
Patch-Clamp Techniques
Periaqueductal Gray cytology
Rats
Rats, Sprague-Dawley
Synaptophysin metabolism
Amygdala cytology
Neurons drug effects
Periaqueductal Gray drug effects
Receptors, Opioid, mu drug effects
Synapses drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 312
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 15388784
- Full Text :
- https://doi.org/10.1124/jpet.104.074633