Intrathecal substance P analogue causes motor dysfunction in the rat

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Substance P (SP) is a neuropeptide involved in various physiological processes, including pain and motor control.
• The specific roles and receptor interactions of modified SP analogs are not fully elucidated.

Purpose of the Study:

• To investigate the effects of (D-Pro2, Trp7,9)-substance P (DPDT-SP) on motor function in rats.
• To determine the involvement of opioid and SP receptors in the motor dysfunction induced by DPDT-SP.

Main Methods:

• Administration of DPDT-SP into the subarachnoid space in rats.
• Dose-response assessment of induced motor dysfunction.
• Evaluation of the effects of naloxone (opioid receptor antagonist) and intrathecal SP on motor function.
• Measurement of SP levels in the lumbar cord.

Main Results:

• DPDT-SP induced severe, dose-related flaccid hindlimb extension (paralysis).
• Naloxone and intrathecal SP failed to reverse the DPDT-SP-induced motor dysfunction.
• SP levels were significantly depleted in the lumbar cord of paralyzed rats.

Conclusions:

• DPDT-SP causes significant motor dysfunction in rats.
• The mechanism of DPDT-SP-induced motor dysfunction does not appear to involve opioid or SP receptors.
• SP depletion in the spinal cord may be a consequence of DPDT-SP administration.