Effects of neonatal stress and morphine on kappa opioid receptor signaling

Thuy N Vien1, Christine A Gleason, Sarah L Hays

  • 1Department of Pediatrics, University of Washington, Seattle, WA 98195-6320, USA. sjuul@u.washington.edu

Neonatology
|May 30, 2009
PubMed

Insights

Neonatal stress activates the kappa opioid receptor (KOR) system in mice, particularly when combined with morphine. This stress response involves the dynorphin system and can lead to inflammation in the brain.

Area of Science:

  • Neuroscience
  • Neonatal Research
  • Pharmacology

Background:

  • Critically ill neonates face significant stressors, often managed with opioids.
  • Long-term effects of neonatal stress and opioid exposure remain unclear.
  • The role of the kappa opioid system in neonatal stress is largely unknown.

Purpose of the Study:

  • To map kappa opioid receptor (KOR) distribution in the neonatal mouse brain.
  • To investigate how neonatal morphine, stress, or combined exposure alters KOR signaling.

Main Methods:

  • Utilized wild-type and prodynorphin (Pdyn) knockout mouse models.
  • Administered saline, morphine, or stress (with saline/morphine) from postnatal days 5-9.
  • Examined brain tissue using KOR-P, GFAP, and GAD immunolabeling.

Main Results:

  • Neonatal stress increased KOR-P in wild-type mice but not Pdyn(-/-) mice.
  • Combined stress and morphine significantly elevated KOR-P (38-500%) and caused gliosis.
  • Pdyn(-/-) mice showed increased gliosis even without KOR-P signaling.

Conclusions:

  • Neonatal stress activates KOR through the dynorphin system.
  • Co-exposure to stress and morphine exacerbates KOR activation and induces hippocampal gliosis.
  • Endogenous dynorphin may mitigate stress-induced inflammatory responses.
Abstract

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...