NMDA-NR1 RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN RAT-BRAIN AFTER6-OH-DOPAMINE INDUCED LESIONS - A NONISOTOPIC IN-SITU HYBRIDIZATION STUDY

Antisense digoxigenin-labeled deoxyoligonucleotides probes and non-iso topic in situ hybridization (HIS) techniques have been used to explore the NMDA-NR1 receptor subunit mRNA distribution in different brain ar eas of rats which had their dopaminergic nigrostriatal pathway previou sly lesioned with intracerebral administration of 6-OH-dopamine (6-OH- DA), Intense and significant hybridization signals for NR1 mRNA were f ound in dentate gyrus and regions CA(1)-CA(2)-CA(3) of the hippocampus , in layers II-III and V-VI of the cerebral cortex, and in the cerebel lum of sham-treated rats, Basal ganglia structures such as the striatu m exhibited few NR1 mRNA hybridization signals as compared to the hipp ocampus and cerebral cortex, In contract, both zona compacta and retic ulata of substantia nigra (SN) showed a reduced number of cells with n evertheless intense NR1 mRNA HIS signals, The NR1 mRNA distribution in the brain was affected in a brain regional selective manner by 6-OH-D A induced lesions of DA neuronal systems, A striking increase in NR1 m RNA HIS signals was observed in both striata after unilateral lesionin g with 6-OH-DA, Instead, in SN compacta but not in reticulata, a moder ate but significant bilateral reduction of NR1 mRNA was observed after unilateral 6-OH-DA injection. No significant changes in NR1 mRNA were detected in cerebral cortex and other brain regions after 6-OH-DA tre atment, These studies, and others reported in the literature, support the view that extensive lesions of nigrostriatal DA-containing neurons in the brain may trigger compensatory or adaptative responses in basa l ganglia structures such as striatum and substantia nigra which invol ve glutamatergic neurons and the genic expression of NMDA receptors. ( C) 1996 Wiley-Liss, Inc.