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Tolerance and sensitization to the heart-rate effects of morphine
1Department of Medical Psychology, Oregon Health Sciences University, Portland 97201.
Abstract:
The effect of daily exposure to one of several doses of morphine (0, 2.0, 4.0 and 8.0 mg/kg IV) on heart rate was assessed in restrained (R) and unrestrained (U) rats. Initially, morphine produced a biphasic heart-rate response; bradycardia followed by tachycardia. Tolerance to the bradycardic effect was established in the 4 and 8 mg/kg U groups and in the 2 and 4 mg/kg U groups. Sensitization developed to the tachycardic effect in the 2 and 4 mg/kg U groups but not in the 8 mg/kg U group or any of the R groups. After several exposures to morphine, mean preinfusion heart rate increased in the 4 and 8 mg/kg dose groups but not in the 0 and 2 mg/kg dose groups. These results are generally consistent with the other data suggesting that tolerance develops only to the depressant effects of morphine, and either no change or sensitization develops to its stimulant effects. The development of higher preinfusion heart rates in the higher dose groups may represent a learned anticipatory response.
Insights
Rats developed tolerance to morphine
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Morphine is an opioid analgesic with complex cardiovascular effects.
- Understanding tolerance and sensitization to morphine is crucial for clinical use.
Purpose of the Study:
- To investigate the development of tolerance and sensitization to morphine's heart rate effects in rats.
- To examine the influence of restraint stress on these adaptations.
Main Methods:
- Rats received daily intravenous doses of morphine (0, 2.0, 4.0, 8.0 mg/kg) under restrained and unrestrained conditions.
- Heart rate responses (bradycardia, tachycardia) and preinfusion heart rates were monitored over several exposures.
Main Results:
- Morphine initially caused biphasic heart rate changes: bradycardia then tachycardia.
- Tolerance to bradycardia occurred in higher dose unrestrained groups.
- Sensitization to tachycardia occurred in lower-to-moderate dose unrestrained groups, but not in the highest dose or restrained groups.
- Preinfusion heart rate increased in higher dose groups, suggesting a learned anticipatory response.
Conclusions:
- Tolerance to morphine's depressant effects (bradycardia) develops, while stimulant effects (tachycardia) may lead to sensitization or no change.
- Restraint stress may inhibit the development of tolerance and sensitization.
- Learned anticipatory responses might contribute to altered heart rate patterns with repeated morphine exposure.