Cannabinoid modulation of neurotransmission during morphine tolerance

Information

  • Research Project
  • 8525485
  • ApplicationId
    8525485
  • Core Project Number
    F32DA034464
  • Full Project Number
    1F32DA034464-01A1
  • Serial Number
    034464
  • FOA Number
    PA-11-113
  • Sub Project Id
  • Project Start Date
    7/1/2013 - 11 years ago
  • Project End Date
    6/30/2015 - 9 years ago
  • Program Officer Name
    AVILA, ALBERT
  • Budget Start Date
    7/1/2013 - 11 years ago
  • Budget End Date
    6/30/2014 - 10 years ago
  • Fiscal Year
    2013
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    6/3/2013 - 11 years ago
Organizations

Cannabinoid modulation of neurotransmission during morphine tolerance

DESCRIPTION (provided by applicant): Opioids such as morphine are among the most important tools used to treat pain, however their use is limited due to the development of tolerance and other negative side effects. Cannabinoids such as ¿9- tetrahydracannabinol (THC) are also used for pain relief, however their low efficacy and side effects also limit their clinical utility. Opioids and cannabinoids interact in several ways to produce better pain relief than either drug alone. Recent clinical data in humans demonstrates that cannabinoid administration can improve pain relief in patients already taking opioids for chronic pain. Our preliminary data supports these findings, and suggests that this effect is at least partially mediated by the midbrain periaqueductal gray (PAG). The PAG is critically involved in descending pain modulation and the development of morphine tolerance. The goal of the proposed studies is to elucidate the cellular adaptations in cannabinoid signaling and neurotransmission that occur in the PAG after the development of opioid tolerance. The following two Specific Aims will address these goals, using in vitro electrophysiology techniques: 1) Characterize the changes in cannabinoid-mediated synaptic transmission after chronic morphine exposure. 2) Determine the cellular mechanisms underlying morphine tolerance-induced changes in cannabinoid modulation of neurotransmission in the PAG. The experiments in Aims 1 and 2 will employ whole-cell patch clamp techniques to measure changes in synaptic transmission after chronic opioid exposure, and to determine the molecular mechanisms underlying these changes. Behavioural testing in rats will also be employed to assess antinociception, and verify the development of morphine tolerance. The proposed studies will identify the molecular mechanisms underlying the changes that occur following chronic opioid treatment, in a brain region that is critically involved in opioid tolerance. The field of opioid/cannabinoid interaction is still developing, and characterizing the physiology of this system will have a significant impact on the field. Full understanding of this interaction is critial to our long-term goal of identifying cannabinoid-related cellular targets that may be used to overcome tolerance and improve the analgesic efficacy of opioids. Such an innovation could lead to a major advance in clinical pain management.

IC Name
NATIONAL INSTITUTE ON DRUG ABUSE
  • Activity
    F32
  • Administering IC
    DA
  • Application Type
    1
  • Direct Cost Amount
    41364
  • Indirect Cost Amount
  • Total Cost
    41364
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    279
  • Ed Inst. Type
  • Funding ICs
    NIDA:41364\
  • Funding Mechanism
    TRAINING, INDIVIDUAL
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY OF SYDNEY
  • Organization Department
  • Organization DUNS
    752389338
  • Organization City
    SYDNEY
  • Organization State
  • Organization Country
    AUSTRALIA
  • Organization Zip Code
    2006
  • Organization District
    AUSTRALIA