A study of tolerance to apomorphine

Area of Science:

• Pharmacology
• Neuroscience
• Veterinary Medicine

Background:

• Apomorphine is a dopamine receptor agonist with various physiological effects.
• Understanding tolerance to apomorphine is crucial for its therapeutic applications and managing side effects.

Purpose of the Study:

• To investigate the development of tolerance to the cardiovascular, thermoregulatory, and emetic effects of apomorphine.
• To determine the time course of tolerance to repeated apomorphine administration in anesthetized dogs.

Main Methods:

• Four groups of chloralose-anesthetized dogs received an initial intravenous bolus of apomorphine (200 µg/kg) or saline.
• Subsequent apomorphine administration occurred at 30, 120, or 720 minutes to assess tolerance.
• Changes in blood pressure, heart rate, rectal temperature, respiratory rate, plasma noradrenaline, and emesis were monitored.

Main Results:

• The first apomorphine dose significantly decreased blood pressure and temperature, increased heart rate, and caused emesis in 71% of dogs.
• Tolerance to cardiovascular effects (blood pressure, heart rate) developed within 30 minutes.
• Tolerance to hypothermic and emetic effects showed a slower onset, with significant differences observed at 120 and 720 minutes.

Conclusions:

• Tolerance to apomorphine's cardiovascular, hypothermic, and emetic effects was demonstrated.
• The time course of tolerance varies, with faster development for cardiovascular and emetic effects compared to hypothermic effects.
• These findings suggest tissue-specific regulation of dopamine D2 receptors in response to repeated apomorphine exposure.