Cellular mechanisms of opioid tolerance and dependence

Summary

Tolerance and dependence that contribute to opioid addiction will be studied using patch clamp analyses of cellular and synaptic electrophysiology in brain slices and behavioural correlations.

Supervisor(s)

Professor Macdonald Christie

Research Location

Camperdown - School of Medical Sciences

Program Type

Masters/PHD

Synopsis

Morphine and related opioid drugs very effectively relieve many (but not all) kinds of pain but they often lose their efficacy after prolonged treatment (tolerance).  We have established that loss of opioid receptor function is associated with tolerance but this precedes receptor trafficking mechanisms thought previously by other researchers to be pivotal for tolerance.  Long-term medication with opioids also produces physical dependence (and addiction in some people), which contributes to tolerance and causes a painful and dysphoric withdrawal syndrome upon cessation of treatment.  We know this is due to mechanisms in some nerve cells that attempt to balance their electrical and biochemical activity in the face of continuous inhibition by opioids.  We have now identified one of the key molecular targets in this process, the GAT-1 GABA transporter. In future, new drugs that target this molecule may in lessen opioid tolerance, alleviate withdrawal, or even assist with recovery from opioid addiction.  This project will determine the mechanisms of loss of opioid receptor function and induction of novel signalling mechanisms in nerve cells after chronic morphine treatment using brain slices and heterologous receptor expression systems.

Additional Information

As part of PMRI and the Kolling Institute you would have access to state of the art electrophysiological, molecular biological and optical techniques and be part of the largest group of scientists dedicated to the study of pain in Australia. 

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Keywords

analgesics, Addiction, Pain, addiction tolerance, dependence, opioids, ion channels, sensory neuron, spinal cord, Therapeutics & adverse drug effects, Pain & Trauma, Neuroscience & psychology, Pharmacology & therapeutics

Opportunity ID

The opportunity ID for this research opportunity is: 150

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