Both zimelidine and clorgyline decrease preprotachykinin mRNA in adult medullary raphe nuclei.
Neurons of the medullary raphe nuclei contain multiple neurotransmitters including the monoamine neurotransmitter serotonin (5-HT) and the tachykinin substance P (SP). Previously, we showed that inhibition of serotonin synthesis increased levels of mRNA coding for preprotachykinin (PPT), the prohormone precursor of SP (P. D. Walker et al., 1990, Mol. Brain Res. 8: 113-119). To determine whether augmented serotonin transmission would have the predictably opposite effect, we have examined the effects of a 5-HT uptake blocker (zimelidine) and a monoamine oxidase inhibitor (clorgyline) on levels of PPT mRNA. We looked also at the effect of zimelidine and clorgyline on levels of ventral spinal cord substance P-like immunoreactivity (SP-LI) of the same animals. Both zimelidine and clorgyline decreased levels of PPT mRNA in medullary raphe neurons and SP-LI in the ventral spinal cord. The effect on message was transient with levels returning to control by 14 days of drug treatment. These results show that increases in synaptic 5-HT cause transient decreases in PPT mRNA and SP-LI.
Riley
L A
LA
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102 USA.
Hart
R P
RP
Jonakait
G M
GM