CHRONIC TREATMENT WITH DIZOCILPINE MALEATE INCREASES THE NUMBER OF STRIATAL NEURONS EXPRESSING THE D-2 RECEPTOR GENE

N-methyl-D-aspartate antagonists have been proposed as potential thera peutic 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 malea te (0.8 mg/kg day, per os for 50 days) were analysed in rat striata. U sing quantitative in situ hybridization, we measured the messenger RNA expression of the genes encoding D-1, D-2 dopamine receptors, N-methy l-D-aspartate receptor 1 subunit of N-methyl-D-aspartate receptor, pre proenkephalin A and substance P. Chronic treatment with dizocilpine ma leate induced a moderate but significant increase in messenger RNA of the N-methyl-D-aspartate receptor 1 subunit in the striatum and the ad jacent cortex, suggesting an action of dizocilpine maleate in these tw o regions. This treatment did not induce any change in D-1 receptor, p reproenkephalin A or substance P messenger RNA content in the striatum , whereas D, receptor messenger RNA was increased in the striatum of t reated rats. Microscopic analysis revealed that it was the number of m edium-sized neurons expressing D-2 receptor messenger RNA that was sig nificantly enhanced, while the mean amount of message per cell remaine d unchanged. These results demonstrate that glutamate via N-methyl-D-a spartate receptors, regulates the D-2 receptor gene in striatal neuron s. A chronic treatment with dizocilpine maleate increases the number o f striatal neurons expressing the D-2 receptor gene, suggesting a recr uiting phenomenon.