Related Experiment Video

Updated: Aug 17, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

Constitutively active micro opioid receptors mediate the enhanced conditioned aversive effect of naloxone in

James R Shoblock1, Nigel T Maidment

  • 1Department of Psychiatry and Biobehavioral Science, University of California Los Angeles, Los Angeles, CA 90024, USA. shoblock@ucla.edu

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|June 16, 2005
PubMed

Insights

Morphine exposure enhances naloxone

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Naloxone causes aversion in rodents by blocking mu opioid receptors.
  • Morphine pre-exposure potentiates this naloxone-induced aversion.
  • Morphine may increase constitutive activity of mu opioid receptors.

Purpose of the Study:

  • To investigate if enhanced mu opioid receptor constitutive activity underlies naloxone's potentiated aversion after morphine exposure.
  • To compare naloxone's effects with neutral antagonists (6-alpha- and 6-beta-naloxol) in mice with and without prior morphine exposure.

Main Methods:

  • Conditioned Place Aversion (CPA) testing in mice.
  • Administration of naloxone, 6-alpha-naloxol, and 6-beta-naloxol.
  • Prior morphine exposure at varying intervals before antagonist administration.

Main Results:

  • All tested drugs produced CPA.
  • Morphine pre-exposure selectively enhanced naloxone-induced CPA.
  • Only naloxone precipitated withdrawal jumping at 20 hours post-morphine, unlike 6-alpha-naloxol at 4 hours.

Conclusions:

  • Morphine enhances naloxone's aversive effects by increasing constitutively active mu opioid receptors.
  • Constitutive mu opioid receptor activity plays a role in naloxone-precipitated withdrawal.
  • Long-term changes in mu receptor activity from opiate exposure may contribute to addiction-related dysregulation.

More Related Videos

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats04:11

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats

Published on: November 6, 2018

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents07:05

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents

Published on: September 10, 2018

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...
Drug Abuse and Addiction: Pharmacological Phenomena01:15

Drug Abuse and Addiction: Pharmacological Phenomena

Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not necessarily...
Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents01:17

Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents

Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down...