MK-801 prevents dopamine DI 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 i n organotypic slice cultures. A 3 h exposure to SKF-38393 (10 muM, DA D-1 a gonist) or DOI (10 muM, 5-HT2 agonist) increased PPT mRNA levels to 196.4% and 154.0%, respectively. Responses to SKF-38393 were prevented by SCH-2339 0(10 muM D-1 antagonist) whereas DOI-stimulated increases were prevented by ketanserin (10 muM, 5-HT2A antagonist). Since striatal tachykinin neurons also possess NMDA receptors that regulate gene expression, stimulation of P PT 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 P PT message levels. However, MK-801 prevented SKF-38393-stimulated increases in PPT mRNA expression while DOI-induced expression was not affected. Thes e results provide evidence that D-1 regulation of striatal tachykinin expre ssion is dependent on NMDA-type glutamate neurotransmission while 5HT(2A) r egulation appears independent. NeuroReport 12:953-955 (C) 2001 Lippincott W illiams & Wilkins.