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The Journal of Neurophysiology Vol. 84 No. 2 August 2000, pp. 744-751
Copyright ©2000 by the American Physiological Society
1Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6; and 2Department of Medicine (Neurology) and Division of Neuroscience, University of Alberta, Edmonton, Alberta T6G 2B7, Canada
Chen, Xihua,
Jeffrey A. Zidichouski,
Kim H. Harris, and
Jack H. Jhamandas.
Synaptic Actions of Neuropeptide FF in the Rat Parabrachial
Nucleus: Interactions With Opioid Receptors. J. Neurophysiol. 84: 744-751, 2000. The pontine parabrachial
nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF)
projections from the lower brain stem and/or the spinal cord. Because
of this anatomical convergence and previous evidence that NPFF displays
both pro- and anti-opioid activities, this study examined the synaptic
effects of NPFF in the PBN and the mechanisms underlying these effects
using an in vitro brain slice preparation and the nystatin-perforated
patch-clamp recording technique. Under voltage-clamp conditions, NPFF
reversibly reduced the evoked excitatory postsynaptic currents (EPSCs)
in a dose-dependent fashion. This effect was not accompanied by
apparent changes in the holding current, the current-voltage
relationship or
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid-induced inward currents in the PBN cells. When a paired-pulse
protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift
in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that
NPFF reduces the evoked EPSCs through a presynaptic mechanism of
action. The synaptic effects induced by NPFF (5 µM) could not be
blocked by the specific µ-opioid receptor antagonist,
D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (1 µM), but application of
-opioid receptor antagonist
Tyr-Tic-Phe-Phe (5 µM) almost completely prevented effects of NPFF.
Moreover, the
-opioid receptor agonist, Deltorphin (1 µM),
mimicked the effects as NPFF and also occluded NPFF's actions on
synaptic currents. These results indicate that NPFF modulates
excitatory synaptic transmission in the PBN through an interaction with
presynaptic
-opioid receptors. These observations provide a cellular
basis for NPFF enhancement of the antinociceptive effects consequent to
central activation of
-opioid receptors.
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