Synaptic actions of neuropeptide FF in the rat parabrachial nucleus: Interactions with opioid receptors

The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptid e FF (NPFF) projections from the lower brain stem and/or the spinal cord. B ecause of this anatomical convergence and previous evidence that NPFF displ ays both pro- and antiopioid activities, this study examined the synaptic e ffects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clam p recording technique. Under voltage-clamp conditions, NPFF reversibly redu ced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holdin g current, the current-voltage relationship or alpha-amino-3-hydroxy-5-meth yl-4-isoxazolepropionic acid-induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synapt ic currents. Analysis of miniature EPSCs showed that NPFF caused a rightwar d shift in the frequency-distribution curve, whereas the amplitude-distribu tion curve remained unchanged. Collectively, these experiments indicate tha t NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 mu M) could not be blocked by the s pecific mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr- NH2 (1 mu M), but application of delta-opioid receptor antagonist Tyr-Tic-P he-Phe (5 mu M) almost completely prevented effects of NPFF. Moreover, the delta-opioid receptor agonist, Deltorphin (1 mu M), 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 th rough an interaction with presynaptic delta-opioid receptors. These observa tions provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of delta-opioid receptors.