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Both zimelidine and clorgyline decrease preprotachykinin mRNA in adult medullary raphe nuclei.

L A Riley¹, R P Hart, G M Jonakait

¹Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102 USA.

Molecular and Cellular Neurosciences

|November 17, 2009

Summary

This summary is machine-generated.

Increased serotonin transmission, using drugs like zimelidine and clorgyline, temporarily reduces substance P precursor (PPT) mRNA in brainstem neurons and substance P-like immunoreactivity (SP-LI) in the spinal cord.

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Area of Science:

Neuroscience
Neurochemistry
Molecular Biology

Background:

Medullary raphe nuclei neurons co-express serotonin (5-HT) and substance P (SP).
Previous research indicated that inhibiting serotonin synthesis elevates preprotachykinin (PPT) mRNA levels.

Purpose of the Study:

To investigate the effect of enhanced serotonin transmission on PPT mRNA and SP-LI.
To determine if increased synaptic 5-HT levels inversely regulate PPT gene expression and SP levels.

Main Methods:

Administration of a 5-HT uptake blocker (zimelidine) and a monoamine oxidase inhibitor (clorgyline).
Quantification of PPT mRNA levels in medullary raphe neurons.
Measurement of ventral spinal cord substance P-like immunoreactivity (SP-LI).

Main Results:

Both zimelidine and clorgyline treatments led to a decrease in PPT mRNA levels.
These treatments also reduced SP-LI in the ventral spinal cord.
The observed effects on PPT mRNA were transient, with levels normalizing by 14 days.

Conclusions:

Augmented synaptic serotonin transmission causes a temporary reduction in PPT mRNA and SP-LI.
This suggests a regulatory role for serotonin in the expression of the substance P pathway.