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Professor Graeme Henderson

Opioid Drug Action

Our research is aimed at understanding the lethality of opioid drugs such as heroin, methadone and fentanyl in opioid overdose and how their lethality (through depression of respiration) can be enhanced by other drugs such as alcohol and gabapentinoids.

Prolonged use of opioids results in the development of tolerance whereby the effect of the drug (euphoria or respiratory depression) is reduced and more drug must be taken to induce the original level of effect. We have demonstrated that the mechanisms underlying tolerance may be different for different opioids and that alcohol and gabapentinoids lower heroin but not methadone tolerance.

We use a reverse translational approach whereby we interview heroin users to find out their views on the dangers of opioid overdose and how that may be altered by other drugs. We then perform controlled laboratory experiments to examine the cellular mechanisms underlying such interactions.

Research keywords

  • G protein-coupled receptors
  • receptor desensitization and internalization
  • morphine
  • heroin
  • somatostatin

Diseases related to this field of research

  • Drug addiction

Processes and functions relevant to this work

  • Cellular mechanisms underlying the acute action of opioid drugs and the development of tolerance and physical dependence

Equipment relevant to this work

  • Confocal microscopy (MRC imaging facility)
  • fluorescence microscopy
  • electrophysiologial apparatus
  • image analysis software

Research findings

  • Role of kinases in opioid receptor desensitization
  • Somatostatin receptor (sst2b) trafficking
  • differential activation of μ-opioid receptors induces different mechanisms of tolerance Read more >

Collaborations

  • Dr Eamonn Kelly - School of Physiology & Pharmacology