Abstract
BackgroundOpioid 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. MethodsMice 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. ResultsProlonged 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. ConclusionsProlonged 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.