[H-3]CNQX and NMDA-sensitive [H-3]glutamate binding sites and AMPA receptor subunit RNA transcripts in the striatum of normal and weaver mutant mice and effects of ventral mesencephalic grafts

Levels of excitatory amino acid receptors were studied in the weaver mouse model of DA deficiency after unilateral intrastriatal transplantation of E1 2 +/+ mesencephalic cell suspensions. Graft integration was verified by tur ning behavior tests and from the topographical levels of the DA transporter , tagged autoradiographically with 3 nM [H-3]GBR 12935 (average increase in grafted dorsal striatum compared to nongrafted side, 60%). Autoradiography of 80 nM [H-3]CNQX and 100 nM NMDA-sensitive [H-3]glutamate binding was ca rried out to visualize the topography of non-NMDA and NMDA receptors, respe ctively, in +/+ mice and in recipient weaver mutants 3 months after graftin g. Increases of 30% or more were found for [H-3]CNQX binding in the dorsal nongrafted weaver striatum compared to +/+, and a further 6-9% increase in grafted weaver compared to nongrafted side. The added increase of non-NMDA receptors in the transplanted striatum might be explained by a presence of such receptors on DA presynaptic endings of graft origin. A 20% increase in NMDA-sensitive [H-3]glutamate binding was measured in the dorsal nongrafte d weaver striatum compared to +/+. NMDA-sensitive [H-3]glutamate binding in the transplanted side of weaver mutants tended to be slightly higher in al l areas of the striatal complex compared to the nongrafted side, without re aching conventional levels of statistical significance. Using in situ hybri dization histochemistry with synthetic P-32-labeled oligonucleotide probes, we investigated RNA transcripts encoding the four AMPA receptor subunits. RNA transcripts in the striatum are seen with a decreasing signal intensity in the following order: GluRB > GluRA > GluRC > GluRD. The weaver caudate- putamen shows a 12% increase in GluRA subunit mRNA compared to +/+, whereas mesencephalic neuron transplantation leads to slight increases (3%) in the levels of GluRB mRNA in the nucleus accumbens. The results are placed in t he context of the important interaction between the converging glutamatergi c corticostriatal and the DAergic nigrostriatal pathways in controlling the functional output of the basal ganglia in Parkinson's disease and in exper imental models of DA deficiency.