Striatal tachykinin and enkephalin mRNAs are normalized by serotonin2 and NMDA manipulation following dopamine depletion

We have examined the effects of serotonin(2) (5-HT2) stimulation and NMDA antagonism on preprotachykinin (PPT) and preproenkephalin (PPE) gene regulation in the dopamine (DA) depleted striatum. Following DA lesions, PPT mRNA expression was reduced (dorsomedial (DM) 44+/-9%, dorsolateral (DL) 40+/-4%), whereas PPE message levels were elevated (DM 207+/-28%, DL 198+/-25%). Within this state of dysregulated gene activity, DOI (5-HT2 agonist) increased PPT message levels (174+/-5%, DM; 153+13%, DL) without affecting PPE gene expression. In addition, MK-801 (NMDA antagonist) decreased PPE message levels (DM 59+/-10%, DL 52+/-7%) without significantly altering PPT mRNA expression, Combined application of DOI and MK-801 resulted in normalization of both PPT and PPE message. Statistical analysis revealed no drug interactions in this paradigm suggesting independent mechanisms for 5-HT2 and NMDA receptors in controlling neuropeptide production following DA depletion. NeuroReport 13:5-8 (C) 2002 Lippincott Williams Wilkins.