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

Inhibition of morphine tolerance and dependence by MS-153, a glutamate transporter activator

T Nakagawa1, T Ozawa, K Shige

  • 1Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, 606-8501, Kyoto, Japan.

European Journal of Pharmacology
|May 12, 2001
PubMed

Insights

The compound (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) was found to inhibit the development of morphine tolerance and physical dependence in mice. MS-153, a glutamate transporter activator, shows potential for managing opioid-induced side effects.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Morphine tolerance and physical dependence are significant challenges in pain management.
  • Glutamate pathways are implicated in the neurobiological mechanisms underlying opioid dependence.
  • Developing strategies to mitigate these effects is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) on morphine tolerance and physical dependence in a mouse model.
  • To determine if MS-153, a known glutamate uptake enhancer, can modulate the development of opioid-induced side effects.

Main Methods:

  • Mice were treated with morphine to induce tolerance and dependence.
  • Co-administration of MS-153 with morphine was assessed for its impact on acute antinociception.
  • The development of morphine tolerance and physical dependence was evaluated in the presence of MS-153 using behavioral assays and naloxone-precipitated withdrawal signs.

Main Results:

  • MS-153 did not alter the acute antinociceptive potency of morphine.
  • Co-administration of MS-153 significantly attenuated the development of morphine tolerance.
  • MS-153 suppressed naloxone-precipitated withdrawal signs, indicating an inhibition of physical dependence development.

Conclusions:

  • MS-153, a glutamate transporter activator, effectively inhibits the development of morphine tolerance and physical dependence.
  • These findings suggest MS-153 as a potential therapeutic agent to manage opioid-induced tolerance and dependence.
  • Targeting glutamate uptake may be a viable strategy for mitigating adverse effects of chronic opioid use.

More Related Videos

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

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

Related Concept Videos

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...
CNS Depressants: Alcohol and Nicotine01:27

CNS Depressants: Alcohol and Nicotine

Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
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: 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...
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...