NMDA receptor antagonism modifies the synergistic regulation of striatal tachykinin gene expression induced by dopamine D(1) and serotonin(2) receptor stimulation following neonatal dopamine depletion.
Co-application of SKF-38393 (dopamine D(1) agonist; 1 mg/kg) and DOI (serotonin(2) agonist; 1 mg/kg) induced a synergistic increase in striatal preprotachykinin (PPT) mRNA levels in adult rats 60 days after neonatal intracerebroventricular injection of 6-hydroxydopamine. This magnitude of response was not observed in intact (vehicle-injected) rats and was restricted to the dorsomedial (DM, 333+/-25% of lesion) subregion of the anterior striatum, with smaller increases observed in the dorsolateral striatum (DL, 206+/-26% of lesion). A single i.p. injection of MK-801 (NMDA antagonist; 0.1 mg/kg) administered prior to dopamine D(1) (D(1)) and serotonin(2) (5-HT(2)) receptor co-stimulation suppressed the synergistic regulation of PPT mRNA expression in the DM striatum, but also produced a large increase in PPT message levels within the DL striatum (321+/-17% of lesion). These data suggest that the synergistic regulation of PPT mRNA within the DM striatum induced by D(1)/5-HT(2) receptor co-stimulation in the dopamine lesioned rat is dependent on NMDA receptor activity. However, MK-801 may simultaneously potentiate striatal PPT mRNA expression by a separate mechanism due to the changed environment of the dopamine-depleted basal ganglia.
Campbell
B M
BM
Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Walker
P D
PD
D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000502:physiology*; D003714:Denervation; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D011985:Receptors, Serotonin / Q000378:metabolism*; D013373:Substance P / Q000235:genetics*; D013565:Sympatholytics
D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D013565:Sympatholytics; D013373:Substance P; D016291:Dizocilpine Maleate; D016627:Oxidopamine; D004298:Dopamine