Chronic treatment with dizocilpine maleate increases the number of striatal neurons expressing the D2 receptor gene.
N-methyl-D-aspartate antagonists have been proposed as potential therapeutic agents in different neurological diseases, including Parkinson's disease. The effects of gene expression of a chronic treatment with the non-competitive N-methyl-D-aspartate antagonist, dizocilpine maleate (0.8 mg/kg day, per os for 50 days) were analysed in rat striata. Using quantitative in situ hybridization, we measured the messenger RNA expression of the genes encoding D1, D2 dopamine receptors, N-methyl-D-aspartate receptor 1 subunit of N-methyl-D-aspartate receptor, preproenkephalin A and substance P. Chronic treatment with dizocilpine maleate induced a moderate but significant increase in messenger RNA of the N-methyl-D-aspartate receptor 1 subunit in the striatum and the adjacent cortex, suggesting an action of dizocilpine maleate in these two regions. This treatment did not induce any change in D1 receptor, preproenkephalin A or substance P messenger RNA content in the striatum, whereas D2 receptor messenger RNA was increased in the striatum of treated rats. Microscopic analysis revealed that it was the number of medium-sized neurons expressing D2 receptor messenger RNA that was significantly enhanced, while the mean amount of message per cell remained unchanged. These results demonstrate that glutamate via N-methyl-D-aspartate receptors, regulates the D2 receptor gene in striatal neurons. A chronic treatment with dizocilpine maleate increases the number of striatal neurons expressing the D2 receptor gene, suggesting a recruiting phenomenon.
Lannes
B
B
Institut de Physiologie, Faculté de Médecine, Strasbourg, France.
Bernard
V
V
Bloch
B
B
Micheletti
G
G
D000818:Animals; D015342:DNA Probes; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004745:Enkephalins / Q000096:biosynthesis; D017403:In Situ Hybridization; D008297:Male; D017072:Neostriatum / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009714:Nucleus Accumbens / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013373:Substance P / Q000096:biosynthesis
D015342:DNA Probes; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; D016291:Dizocilpine Maleate; C033660:preproenkephalin