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Morphine-ethanol interaction on body temperature
A Orts1, C Alcaraz, L Goldfrank
1Department of Anesthesiology, New York University Medical Center, NY 10016.
Abstract:
1. The interaction between ethanol and morphine on core temperature was investigated in Swiss Webster mice. 2. Morphine (2.5-30 mg/kg) and ethanol (0.5-3.0 mg/g) administered individually resulted in a dose dependent decrease in body temperature. 3. When both drugs were injected simultaneously, body temperature decreased less than it would be expected to if the effects were additive. 4. Naloxone antagonized the hypothermic effect of morphine, but the hypothermic effect of ethanol and that of the combination of morphine plus ethanol was only reversed with high doses of naloxone (10 mg/kg). 5. Individual morphine and ethanol plasma levels were not significantly altered by their concomitant administration. 6. Binding of tritiated naloxone to opiate receptors in mouse brain membrane preparations was unchanged by pretreatment with ethanol (0.5 and 2 mg/g). 7. The interaction between morphine and ethanol was found to be less than additive and not related to pharmacokinetic changes of either drug.
Insights
Ethanol and morphine both lower mouse body temperature. Their combined effect is less than additive, and not due to changes in drug levels or receptor binding.
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Ethanol and morphine are commonly used substances with known physiological effects.
- Understanding their interaction is crucial for predicting combined effects and potential risks.
Purpose of the Study:
- To investigate the interaction between ethanol and morphine on core body temperature in mice.
- To determine if the hypothermic effects are additive and the role of opioid receptors in this interaction.
Main Methods:
- Swiss Webster mice were administered varying doses of morphine and ethanol, individually and concurrently.
- Core body temperature was monitored, and naloxone was used to assess opioid receptor involvement.
- Plasma drug levels and naloxone binding to opiate receptors were measured.
Main Results:
- Both morphine and ethanol produced dose-dependent hypothermia when administered alone.
- The combined administration of morphine and ethanol resulted in a hypothermic effect that was less than additive.
- High doses of naloxone were required to reverse the hypothermic effects of ethanol and the combination.
- Ethanol did not significantly alter morphine or ethanol plasma levels, nor did it affect naloxone binding to opiate receptors.
Conclusions:
- The interaction between morphine and ethanol on core body temperature is less than additive.
- This interaction is not mediated by pharmacokinetic changes in either drug or by alterations in opiate receptor binding.
- The findings suggest a complex interplay between ethanol and morphine beyond simple additive effects at the opioid receptor level.