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Effect of the {mu} opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala.
J Pharmacol Exp Ther. 2005 Feb; 312(2):441-8.JP

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.

Authors+Show Affiliations

Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15388784

Citation

Finnegan, Thomas F., et al. "Effect of the {mu} Opioid On Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-projecting Neurons in the Amygdala." The Journal of Pharmacology and Experimental Therapeutics, vol. 312, no. 2, 2005, pp. 441-8.
Finnegan TF, Chen SR, Pan HL. Effect of the {mu} opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala. J Pharmacol Exp Ther. 2005;312(2):441-8.
Finnegan, T. F., Chen, S. R., & Pan, H. L. (2005). Effect of the {mu} opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala. The Journal of Pharmacology and Experimental Therapeutics, 312(2), 441-8.
Finnegan TF, Chen SR, Pan HL. Effect of the {mu} Opioid On Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-projecting Neurons in the Amygdala. J Pharmacol Exp Ther. 2005;312(2):441-8. PubMed PMID: 15388784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of the {mu} opioid on excitatory and inhibitory synaptic inputs to periaqueductal gray-projecting neurons in the amygdala. AU - Finnegan,Thomas F, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, Y1 - 2004/09/23/ PY - 2004/9/25/pubmed PY - 2005/3/19/medline PY - 2004/9/25/entrez SP - 441 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 312 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15388784/Effect_of_the_{mu}_opioid_on_excitatory_and_inhibitory_synaptic_inputs_to_periaqueductal_gray_projecting_neurons_in_the_amygdala_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15388784 DB - PRIME DP - Unbound Medicine ER -