Related Experiment Video

Updated: Aug 11, 2025

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

33.5K

Coordinated activity of a central pathway drives associative opioid analgesic tolerance

Yiwen Hou1, Guichang Zou1,2, Xianglian Wang1

  • 1Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.

Science Advances
|February 8, 2023
PubMed

Insights

Associative learning drives opioid tolerance via a specific brain circuit. This pathway involves the ventral hippocampus and prefrontal cortex, offering new targets for treating opioid misuse and overdose.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Opioid analgesic tolerance is a major driver of opioid overdose and misuse.
  • The precise neural circuits underlying associative opioid analgesic tolerance (AOAT) remain largely unknown.

Purpose of the Study:

  • To identify the specific brain regions and pathways involved in AOAT.
  • To elucidate the cellular and circuit mechanisms by which AOAT is established and maintained.

Main Methods:

  • Chemo/optogenetic manipulation
  • Calcium imaging
  • Slice physiology

Main Results:

  • Identified a hierarchically organized pathway essential for AOAT.
  • Demonstrated glutamatergic signaling from the ventral hippocampus (vHPC) to dorsomedial prefrontal cortex (dmPFC) cholecystokininergic (CCKergic) neurons.
  • Showed that CCKergic neurons excite basolateral amygdala (BLA) glutamatergic neurons, inhibiting BLA μ-opioid receptor function and causing tolerance.

Conclusions:

  • Established a distinct neural circuit for opioid analgesic tolerance.
  • Highlighted the role of vHPC-dmPFC-BLA pathway in AOAT.
  • Proposed that components of this pathway are potential therapeutic targets for opioid overdose and abuse.

More Related Videos

Use of the Operant Orofacial Pain Assessment Device OPAD to Measure Changes in Nociceptive Behavior12:20

Use of the Operant Orofacial Pain Assessment Device OPAD to Measure Changes in Nociceptive Behavior

Published on: June 10, 2013

21.3K
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

17.1K

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...
709
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,...
1.3K
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...
323
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...
371
Pain01:20

Pain

Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
536
Nociception01:44

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
28.2K