Related Experiment Video

Updated: Oct 9, 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

Tolerance and cross-tolerance to the response rate-decreasing effects of µ opioids in morphine-maintained squirrel

C.E. Hughes1, M.J. Picker, L.A. Dykstra

  • 1Department of Psychology, University of North Carolina, Chapel Hill, NC 27599-3270, USA.

Behavioural Pharmacology
|December 1, 1995
PubMed

Insights

This study investigated opioid tolerance and cross-tolerance using different mu opioid drugs in squirrel monkeys. Results show varying degrees of cross-tolerance among opioids, with morphine-induced tolerance being most significant.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Drug Addiction Research

Background:

  • Opioid receptors, particularly the mu receptor, are key targets for pain management and addiction.
  • Understanding tolerance and cross-tolerance is crucial for developing effective opioid therapies and managing addiction.

Purpose of the Study:

  • To quantify the tolerance and cross-tolerance to the effects of various mu-opioid agonists with differing intrinsic efficacies.
  • To compare the development of tolerance to morphine with cross-tolerance to other opioids and a non-opioid.

Main Methods:

  • Squirrel monkeys were trained on a fixed-ratio (FR) 30 schedule for food reinforcement.
  • Dose-effect curves were established for buprenorphine, etorphine, l-methadone, morphine, sufentanil, and pentobarbital.
  • Chronic daily morphine administration was used to induce tolerance, and subsequent dose-effect curves were analyzed.

Main Results:

  • Daily morphine administration caused a significant rightward shift (0.9 log units) in the morphine dose-effect curve, indicating tolerance.
  • Cross-tolerance to other mu-opioids (buprenorphine, etorphine, l-methadone, sufentanil) ranged from 0.4 to 0.6 log units.
  • The non-opioid pentobarbital showed inconsistent shifts, suggesting a lack of cross-tolerance.

Conclusions:

  • All tested mu-opioids, regardless of intrinsic efficacy, induced less cross-tolerance than morphine itself.
  • Pentobarbital did not induce significant cross-tolerance, differentiating it from mu-opioid effects.
  • Findings highlight the complex mechanisms of opioid tolerance and cross-tolerance at the mu receptor.

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

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies08:16

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Published on: October 6, 2022

Related Concept Videos

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 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...
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...
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
Several...
Dose Response Curve: Conventional Versus Nonmonotonic01:21

Dose Response Curve: Conventional Versus Nonmonotonic

The correlation between a drug's dosage and its impact on a biological system is a cornerstone of pharmacology and toxicology. Conventional dose–response curves, which include graded and quantal relationships, are key to this understanding. Graded dose–response curves depict the spectrum of a biological reaction to different doses within an individual, indicating that as the drug dosage increases, so does the intensity of the response. On the other hand, quantal dose–response relationships...