Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala

Introduction: Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. However, side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. Currently, the kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. The purpose of this study was to evaluate the antinociceptive effect of the novel compound - RU-1205. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Results: RU-1205 exhibited highly potent antinociceptive effects in rodent models of acute pain with ED50 values of 0.002 - 0.49 mg /kg. Pretreatment with the κ-opioid receptor antagonist norBinaltorphimine significantly attenuated the analgesic activity of investigated substance in a hot plate test. Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205.

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Signaling Events Initiated by Kappa Opioid Receptor Activation: Quantification and Immunocolocalization Using Phospho-Selective KOR, p38 MAPK, and KIR 3.1 Antibodies

Methods in Molecular Biology - Signal Transduction Immunohistochemistry ◽

10.1007/978-1-61779-024-9_11 ◽

2011 ◽

pp. 197-219 ◽

Cited By ~ 7

Author(s):

Julia C. Lemos ◽

Clarisse A. Roth ◽

Charles Chavkin

Keyword(s):

P38 Mapk ◽

Opioid Receptor ◽

Receptor Activation ◽

Kappa Opioid Receptor ◽

Kappa Opioid ◽

Signaling Events

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Dissociable Effects of Kappa-Opioid Receptor Activation on Impulsive Phenotypes in Wistar Rats

Neuropsychopharmacology ◽

10.1038/npp.2013.129 ◽

2013 ◽

Vol 38 (11) ◽

pp. 2278-2285 ◽

Cited By ~ 19

Author(s):

Brendan M Walker ◽

Jessica L Kissler

Keyword(s):

Opioid Receptor ◽

Wistar Rats ◽

Receptor Activation ◽

Kappa Opioid Receptor ◽

Kappa Opioid

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Neurotensin and Dynorphin Bi-Directionally Modulates CeA Inhibition of oval BNST Neurons in Male Mice

10.1101/367649 ◽

2018 ◽

Author(s):

CP Normandeau ◽

ML Torruella Suárez ◽

P Sarret ◽

ZA McElligott ◽

EC Dumont

Keyword(s):

Opioid Receptor ◽

Neural Circuit ◽

Brain Slices ◽

Kappa Opioid Receptor ◽

Male Mice ◽

Central Amygdala ◽

Kappa Opioid ◽

Brain Circuit ◽

Circuit Function ◽

The Way

AbstractNeuropeptides are often co-expressed in neurons but their neurophysiological effects are commonly studied individually. Multiple neuropeptides may therefore be simultaneously released to coordinate proper neural circuit function. Here, we triggered the release of endogenous neuropeptides in brain slices from male mice to better understand the modulation of central amygdala (CeA) inhibitory inputs onto oval (ov) BNST neurons. We found that locally-released neurotensin (NT) and dynorphin (Dyn) antagonistically regulated CeA inhibitory inputs onto ovBNST neurons. NT and Dyn respectively increased and decreased CeA-to-ovBNST inhibitory inputs through NT receptor 1 (NTR1) and kappa opioid receptor (KOR). Additionally, NT and Dyn mRNAs were highly co-localized in ovBNST neurons suggesting that they may be released from the same cells. Together, we showed that NT and Dyn are key modulators of CeA inputs to ovBNST, paving the way to determine whether different conditions or states can alter the neuropeptidergic regulation of this particular brain circuit.

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