Striatal tachykinin and enkephalin mRNAs are normalized by serotonin2 and NMDA manipulation following dopamine depletion.
We have examined the effects of serotonin2 (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 PPTand 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.
Campbell
Brian M
BM
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Walker
Paul D
PD
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency*; D004745:Enkephalins / Q000235:genetics*; D008297:Male; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012016:Reference Values; D015320:Tachykinins / Q000235:genetics*
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D015320:Tachykinins; C044206:preprotachykinin; C033660:preproenkephalin; D004298:Dopamine