Skip to content

Prolonged ethanol administration prevents the development of tolerance to morphine-induced respiratory depression

Research output: Contribution to journalArticle

Original languageEnglish
Article number107674
Number of pages8
JournalDrug and Alcohol Dependence
Early online date30 Oct 2019
DateAccepted/In press - 1 Oct 2019
DateE-pub ahead of print - 30 Oct 2019
DatePublished (current) - 1 Dec 2019


Background: Opioid users regularly consume other drugs such as alcohol (ethanol). Acute administration of ethanol can rapidly reverse tolerance to morphine-induced respiratory depression. However, alcohol consumption by opioid users is likely to occur over prolonged time periods. We have therefore sought to determine the effect of prolonged alcohol consumption on the development of tolerance to opioid respiratory depression.

Methods: Mice were fed control or ethanol (5%) liquid diet for 16 days. On days 9–16 morphine tolerance was induced by administration of 3 priming injections of morphine followed by subcutaneous implantation of a morphine-filled osmotic mini-pump. Control mice received saline. Respiration was measured by plethysmography and the effect of an acute morphine challenge dose was measured on day 16 to assess the development of morphine tolerance.

Results: Prolonged ethanol consumption for 14 days did not alter the respiratory depressant effect of an acute dose of morphine. Control mice treated with prolonged morphine developed tolerance to acute morphine respiratory depression whereas ethanol diet fed mice treated with prolonged morphine showed significant respiratory depression during morphine-pump treatment and remained sensitive to the respiratory depressant effect of the acute challenge dose of morphine. The ethanol consumption did not alter blood or brain levels of morphine, whilst conversely prolonged morphine treatment did not alter blood levels of ethanol.

Conclusions: Prolonged ethanol consumption prevents the development and maintenance of tolerance to the respiratory depressant effect of morphine. These data suggest that ethanol inhibition of tolerance will greatly increase the risk of fatal heroin overdose in humans.

    Research areas

  • Ethanol, Morphine, Overdose, Respiratory depression, Tolerance



  • Ethanol_mansucript_Final_plus_figures

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at [insert hyperlink] . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 272 KB, PDF document

    Embargo ends: 30/10/20

    Request copy

    Licence: CC BY-NC-ND


View research connections

Related faculties, schools or groups