Pre- and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro

Paul J. Emmerson, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

1. Using whole-cell patch clamp recording from neurones in an in vitro slice preparation, we have examined opioid- and orphanin FQ (OFQ)-mediated modulation of synaptic transmission in the rat arcuate nucleus and ventromedial hypothalamus (VMH). 2. Application of OFQ activated a Ba2+-sensitive and inwardly rectifying K+ conductance in ~ 50% of arcuate nucleus neurones and ~ 95% of VMH neurones. The OFQ-activated current was blocked by the nociceptin antagonist [Phe1Ψ/(CH2NH)Gly2]-nociceptin (1-13) NH2 (NCA), a peptide that on its own exhibited only weak agonist activity at high concentrations (> 1 μM). Similar current activation was observed with the μ agonist DAMGO but not δ (DPDPE) or κ (U69593) agonists. 3. In arcuate nucleus neurones, DAMGO (1 μM), U69593 (1 μM) and OFQ (100 nM to 1 μM) but not DPDPE (1 μM) were found to depress the amplitude of electrically evoked glutamatergic postsynaptic currents (EPSCs) and decrease the magnitude of paired-pulse depression, indicating that opioid receptors were located presynaptically. 4. In VMH neurones, DAMGO strongly depressed the EPSC amplitude in all cells examined. DAMGO decreased the magnitude of paired-pulse depression, indicating that μ receptors were located presynaptically. U69593 weakly depressed the EPSC while OFQ and DPDPE had no effect. 5. In VMH neurones, DAMGO depressed the frequency of miniature EPSCs (-58%) in the presence of tetrodotoxin and Cd2+ (100 μM), suggesting that the actions of μ receptors could be mediated by an inhibition of the synaptic vesicle release process downstream of Ca2+ entry. 6. The data presented show that presynaptic modulation of excitatory neurotransmission in the arcuate nucleus occurs through μ, κ and the orphan opioid ORL-1 receptors while in the VMH presynaptic modulation only occurs through μ opioid receptors. Additionally, postsynaptic μ and ORL-1 receptors in both the arcuate nucleus and VMH modulate neuronal excitability through activation of a K+ conductance.

Original languageEnglish (US)
Pages (from-to)431-445
Number of pages15
JournalJournal of Physiology
Volume517
Issue number2
DOIs
StatePublished - Jun 1 1999

ASJC Scopus subject areas

  • Physiology

Fingerprint

Dive into the research topics of 'Pre- and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro'. Together they form a unique fingerprint.

Cite this