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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on September 23, 2004; DOI: 10.1124/jpet.104.074633


0022-3565/05/3122-441-448$20.00
JPET 312:441-448, 2005
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NEUROPHARMACOLOGY

Effect of the µ Opioid on Excitatory and Inhibitory Synaptic Inputs to Periaqueductal Gray-Projecting Neurons in the Amygdala

Thomas F. Finnegan, Shao-Rui Chen, and Hui-Lin Pan

Department of Anesthesiology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania

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 µ 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 µ opioid receptor agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO, 1 µM), 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 GABAA 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 µ opioid receptors was colocalized with synaptophysin, a presynaptic marker, in close appositions to labeled CeA neurons. These results suggest that activation of µ opioid receptors on presynaptic terminals primarily attenuates GABAergic synaptic inputs to PAG-projecting neurons in the CeA.


Received July 20, 2004; accepted September 22, 2004.

Address correspondence to: Dr. Hui-Lin Pan, Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033. E-mail: hpan{at}psu.edu




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