Depressor and bradycardic effect following intrathecal injection of [NMePhe3,D-Pro4]morphiceptin in rats

Area of Science:

• Pharmacology
• Neuroscience
• Cardiovascular Physiology

Background:

• Opioid receptors, particularly mu receptors, play a role in cardiovascular regulation.
• The spinal cord is a potential site for opioid-mediated control of blood pressure and heart rate.

Purpose of the Study:

• To investigate the effects of a selective mu receptor agonist, [NMePhe3,D-Pro4] morphiceptin (MC), on blood pressure and heart rate when administered intrathecally.
• To determine the role of spinal mu receptors in mediating these cardiovascular effects.

Main Methods:

• Intrathecal administration of varying doses of [NMePhe3,D-Pro4] morphiceptin (MC) to pentobarbital-anesthetized rats.
• Measurement of mean arterial pressure and heart rate.
• Administration of naloxone to assess receptor antagonism.
• Experiments in bilaterally vagotomized rats and rats under artificial respiration.

Main Results:

• Intrathecal MC caused a dose-dependent decrease in mean arterial pressure and heart rate.
• The maximal depressor and bradycardic effects occurred 1 hour post-injection.
• These effects were completely reversed by intrathecal naloxone.
• The cardiovascular effects of MC were preserved in vagotomized rats and those on artificial respiration.

Conclusions:

• The spinal cord, via mu receptors, exerts significant control over blood pressure and heart rate.
• [NMePhe3,D-Pro4] morphiceptin (MC) acts on spinal mu receptors to produce hypotension and bradycardia.
• These findings highlight the potential of spinal opioid pathways in cardiovascular regulation.