MK-801 prevents dopamine D1 but not serotonin 2A stimulation of striatal preprotachykinin mRNA expression.
We examined dopamine (DA) and serotonin (5-HT) receptor-mediated influences on striatal preprotachykinin (PPT, tachykinin precursor) mRNA regulation in organotypic slice cultures. A 3 h exposure to SKF-38393 (10 microM, DA D1 agonist) or DOI (10 microM, 5-HT2 agonist) increased PPT mRNA levels to 196.4% and 154.0%, respectively. Responses to SKF-38393 were prevented by SCH-23390 (10 microM, D1 antagonist) whereas DOI-stimulated increases were prevented by ketanserin (10 microM, 5-HT2A antagonist). Since striatal tachykinin neurons also possess NMDA receptors that regulate gene expression, stimulation of PPT message levels was examined in the presence of MK-801, a non-competitive NMDA antagonist. Alone, MK-801 (10 nM) did not significantly alter basal PPT message levels. However, MK-801 prevented SKF-38393-stimulated increases in PPT mRNA expression while DOI-induced expression was not affected. These results provide evidence that D1 regulation of striatal tachykinin expression is dependent on NMDA-type glutamate neurotransmission while 5-HT2A regulation appears independent.
Campbell
B M
BM
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Walker
P D
PD
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D015320:Tachykinins / Q000096:biosynthesis*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011498:Protein Precursors; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D015320:Tachykinins; C044206:preprotachykinin; D012701:Serotonin; D016291:Dizocilpine Maleate; D004298:Dopamine