Understanding Opioid Receptors and Addiction

Oct 7, 2024

Lecture Notes: Opioid Receptors and Brain Function

Speaker Introduction

  • Speaker: Dr. Brigitte Kiefer
    • PhD in Organic Chemistry and Biochemistry
    • Professor at McGill University and University of Strasbourg
    • Notable achievements in opioid system research
    • Isolated first gene encoding an opioid receptor
    • Her work has advanced understanding of pain, addiction, and mood disorders
    • Awards: Lounsbury Award, French Academy of Science, L’Oreal UNESCO Award for Women in Science

Lecture Overview

  • Topic: Opioid Receptors and Brain Function
  • Importance due to opioid crisis
  • Aim: Understanding molecular basis of opioid receptors, their role, and targeting them for therapeutic effects

Historical Context

  • Opium: Used for thousands of years for pain relief and euphoria
  • Morphine: Isolated active ingredient of opium, effective analgesic but addictive
  • Heroin: Developed by Bayer, initially thought non-addictive, more addictive than morphine
  • Opioid Crisis: Overprescription leading to addiction and overdose deaths

Opioid System

  • Receptors: Mu, Delta, Kappa
  • Endogenous Peptides: Met-enkephalin, Leu-enkephalin, beta-endorphin, dynorphins
  • Receptor Identification: Discovery of genes encoding receptors took 20 years
  • Structure: Solved using X-ray crystallography in 2012

Functions of the Opioid System

  • Reward and Aversion: Regulates beneficial behaviors, stress coping
  • Pain Reduction: Critical in pain and stress coping
  • Autonomic Regulation: Involves immune system, respiration

Research Focus

  1. Mu Opioid Receptor

    • Central to opioid crisis
    • Essential for morphine's effects: analgesia and addiction
    • Exclusively mediates opioid effects
    • Signaling Pathways: G protein and beta-arrestin pathways
  2. Delta and Kappa Receptors

    • Delta: Potential anxiolytic and antidepressant roles
    • Kappa: Induces dysphoria, involved in stress responses
  3. Addiction and Neural Circuits

    • Drug Addiction Cycle: Binge, Withdrawal, Craving
    • Mu receptor critical in addiction initiation
    • Kappa receptor in withdrawal mood states
  4. Innovative Approaches

    • Biased Agonism: Developing drugs targeting specific pathways (e.g., GIGO, beta-arrestin)
    • Virtual Docking: Accelerating drug discovery
    • Translational Neuroimaging: Understanding receptor impact on brain connectivity

Methodological Advances

  • Development of mice with visible receptors for real-time study
  • Impact of receptor knockout studies to understand receptor-specific functions
  • Habenula: Role in aversion, new insights into mu receptor function
  • Mu Receptors in Serotonin Centers: Influence on mood and social behavior

Conclusion

  • Emphasis on the complexity of the opioid system
  • Strategies to reduce adverse effects of opioids
  • Potential for future research to address addiction and receptor function

Questions and Future Directions

  • Exploration of gene variability and its impact
  • Potential of bivalent ligands and their therapeutic prospects
  • Need for organism-level studies in drug development
  • Emphasis on further study of opioid peptides

Acknowledgements

  • Funding from NIH and other organizations
  • Contributions of her research team

This summary provides an overview of the significant points discussed in Dr. Brigitte Kiefer's lecture on the role of opioid receptors in brain function, focusing on the opioid crisis, receptor biology, signaling pathways, and innovative research methodologies to tackle opioid addiction and its effects.