Neuropeptide FF inhibition of morphine effects in the rat hippocampus.
Opioids have an excitatory effect on CA1 pyramidal neurons in the hippocampus due to the inhibition of gamma-aminobutyric acid (GABA) release from interneurons. Electrophysiologically, this pyramidal cell excitation is mainfest as an increase in extracellularly recorded population spikes, while the reduction in synaptic GABA release is manifest as a decrease in the amplitude of intracellularly recorded inhibitory postsynaptic potentials (IPSPs). Recent studies suggest that some of the behavioral effect of opioids, such as antinociceptin, can be inhibited antiopioid peptides such as neuropeptide FF (NPFF). In the present study, we have used the hippocampal response to opioids to examine the potential interactions between morphine and NPFF in vitro. Morphine alone (20-200 microM) caused reversible concentration-dependent increases in population spikes and decreases in IPSPs. In extracellular experiments, NPFF (1 microM) alone had no effect on population spikes, but significantly and concentration-dependently inhibited the morphine-induced increases in these responses. Intracellular experiments indicated that while NPFF had no effect on IPSP amplitude, or other pyramidal neurons membrane properties (membrane potential, input resistance, afterhyperpolarization, action potential frequency), it significantly reduced the decrease in IPSP amplitude caused by morphine. These results demonstrate that NPFF can attenuate the effects of morphine on population spikes and IPSPs in the hippocampus, and suggest that this effect occurs at a presynaptic site, possibly involving GABAergic interneurons.
Miller
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KK
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Lupica
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CR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009292:Narcotic Antagonists; D009842:Oligopeptides; D009270:Naloxone; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide