D1 dopamine receptor-mediated induction ofzif268 andc-fos in the dopamine-depleted striatum: Differential regulation and independence from NMDA receptors

Abstract

Excitatory amino acid afferents from cerebral cortex and dopamine afferents from the substantia nigra synapse on common projection neurons in the striatum. Activation of D1 dopamine receptors increases immediate early gene expression in the striatum and conductance through the N-methyl-d-aspartate (NMDA) receptor. To examine the contribution of NMDA receptor activation to dopamine receptor-mediated responses, we determined the effects of intrastriatal administration of NMDA antagonists on immediate early gene expression in the striatum and rotational behavior induced by stimulation of the D1 receptor in rats with unilateral dopamine depletions. Systemic administration of SKF 38393 increased c-fos and zif268 mRNAs in the striatum and induced contralateral rotation. Intrastriatal infusion of the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl -1-phosphonic acid caused a dose-dependent attenuation of SKF 38393-induced rotation and partially decreased c-fos mRNA expression. However, D1-mediated increases in zif268 mRNA were not affected, except by the highest concentration of antagonist used (10 mM). Another competitive antagonist, 2-amino-5-phosphonovaleric acid, had similar effects. Like the competitive antagonists, intrastriatal infusion of the non-competitive NMDA antagonist MK-801 partially decreased c-fos, but not zif268, mRNA in the area around the microdialysis probe. However, unlike competitive antagonists, local infusion of 1 mM MK-801 potentiated D1-mediated increases in c-fos and zif268 mRNAs in lateral striatum. These data suggest that 1) some D1 dopamine receptor-mediated effects on striatal function are independent of ongoing NMDA receptor activation, whereas other effects are at least partially mediated by NMDA receptor activity in the striatum, and 2) competitive and non-competitive antagonists of the NMDA receptor differently affect D1-mediated immediate early gene expression in the striatum.

D 2 dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons

“…Many antipsychotic drugs, which are D 2 receptor antagonists, can induce gene expression (9), suggesting that D 2 receptors, like D 1 receptors (10)(11)(12), are important in gene regulation. Previous studies have shown that D 1 and D 2 dopamine receptors synergistically activate immediate early gene expression and locomotion in dopaminedepleted striatum (13,14).…”

“…The results provide a potential molecular mechanism for some long-term effects of D 2 receptors, such as alterations of gene expression. Because D 1 receptors also can phosphorylate and activate CREB (10)(11)(12) and MAPK (38), the present results provide a possible explanation for the synergistic effects of D 1 and D 2 dopamine receptors on immediate early gene induction in striatum (13,14). It remains for future studies to identify downstream targets that are regulated by these signaling cascades.…”

Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

“…eNOS cDNA was then linearized with NcoI and transcribed with T7 (sense) and SP6 (antisense) RNA polymerases and [ 33 P]-UTP. For all in situ hybridizations, probes were prepared and added to hybridization buffer to a final concentration of 1 Â 10 6 cpm/ml, as previously described (Keefe and Gerfen, 1996). Hybridization buffer (100 ml) with probe was applied to each slide containing four brain sections, each slide was covered with a glass coverslip, and slides were hybridized overnight in humid chambers at 55°C.…”

A Postsynaptic Interaction between Dopamine D1and NMDA Receptors Promotes Presynaptic Inhibition in the Rat Nucleus Accumbens via Adenosine Release

“…Physiological and behavioral significance D 1 receptor activation can induce expression of immediate-early genes in the striatum and nucleus accumbens via NMDA receptor-dependent means (Keefe and Gerfen, 1996;Konradi et al, 1996;Wang and McGinty, 1996), and this may contribute to the long-term plastic changes underlying the behavioral sensitization and dependence associated with addictive drugs (Hyman, 1996). However, because these processes involve D 1 receptorstimulated adenylyl cyclase and cAM P-dependent phosphorylation, the effects observed in this study may not be related to these behavioral changes.…”