Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Rob Hill, Abi Lyndon, Sarah Withey, Joanne Roberts, Yvonne Kershaw, John MacLachlan, Anne Lingford-Hughes, Eamonn Kelly, Chris Bailey, Matthew Hickman, Graeme Henderson

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Abstract

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts
regularly consume alcohol (ethanol) and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO2 in air in plethysmograph chambers.
Original languageEnglish
Pages (from-to)762–773
Number of pages12
JournalNeuropsychopharmacology
Volume41
Early online date14 Jul 2015
DOIs
Publication statusPublished - Feb 2016

Keywords

  • ethanol
  • morphine
  • respiratory depression
  • opioids

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    Hill, R., Lyndon, A., Withey, S., Roberts, J., Kershaw, Y., MacLachlan, J., Lingford-Hughes, A., Kelly, E., Bailey, C., Hickman, M., & Henderson, G. (2016). Ethanol reversal of tolerance to the respiratory depressant effects of morphine. Neuropsychopharmacology, 41, 762–773. https://doi.org/10.1038/npp.2015.201