B. Lannes et G. Micheletti, SENSITIZATION OF THE STRIATAL DOPAMINERGIC SYSTEM INDUCED BY CHRONIC ADMINISTRATION OF A GLUTAMATE ANTAGONIST IN THE RAT, Neuroscience and biobehavioral reviews, 21(4), 1997, pp. 417-424
The aim of the present study was to assess in the rat the pharmacologi
cal, biochemical and molecular (including in situ hybridization) conse
quences in the striatum of a prolonged (50 days) treatment with dizoci
lpine maleate (MK-801), an N-methyl-D-aspartate (NMDA) antagonist. We
observed a sensitization-like effect characterized by a behavioural hy
perresponsiveness to an acute injection of haloperidol (0.25 mg/kg), a
dopaminergic antagonist. In rats chronically treated with MK-801, thi
s hyperresponsiveness was associated with an increased D2 receptor (D2
R) density in the striatum. At the transcriptional level, the D2R mRNA
was also enhanced in the striatum. Quantitative in situ hybridization
studies revealed that the number of neurons expressing the D2R mRNA w
as significantly enhanced in treated rats, whereas the mean amount of
message per cell was unchanged. These changes could represent the neur
obiological substrate of the observed sensitization. These results sug
gest that the D2R gene is under glutamate control via NMDA receptor in
striatal neurons. (C) 1997 Elsevier Science Ltd.