Projects per year
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% CO<inf>2</inf> in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths.Neuropsychopharmacology advance online publication, 9 September 2015; doi:10.1038/npp.2015.201.
Original language | English |
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Journal | Neuropsychopharmacology |
Early online date | 9 Sept 2015 |
DOIs | |
Publication status | E-pub ahead of print - 9 Sept 2015 |
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Dive into the research topics of 'Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine'. Together they form a unique fingerprint.Projects
- 3 Finished
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CPRD and Drug Related Mortality
Hickman, M. (Principal Investigator)
1/08/14 → 31/01/17
Project: Research
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How does ethanol reverse opioid tolerance?
Henderson, G. (Principal Investigator)
1/06/12 → 1/06/15
Project: Research
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Do biased agonists at the mu-opioid receptor induce different patterns of receptor phosphorylation?
Kelly, E. P. (Principal Investigator)
1/03/12 → 1/03/15
Project: Research
Profiles
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Professor Graeme Henderson
Person: Academic , Member
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Professor Eamonn P Kelly
- School of Physiology, Pharmacology & Neuroscience - Professor of Molecular Pharmacology
Person: Academic