Effects of neonatal 6-hydroxydopamine injections on glutamate decarboxylase, preproenkephalin and dopamine D2 receptor mRNAs in the adult rat striatum.

The effects of neonatal 6-hydroxydopamine injections on the levels and cellular distribution of glutamate decarboxylase (GAD67), preproenkephalin and dopamine D2 receptor messenger RNAs were studied in the striatum of adult rats. Cerebroventricular injections of 150 micrograms or 100 micrograms of 6-hydroxydopamine to 3-day-old neonate rats resulted in the total disappearance of neurons labeled with a tyrosine hydroxylase probe in sections of the substantia nigra and ventral tegmental area. In the striatum of adults, both doses of 6-hydroxydopamine induced an increase in GAD67 and preproenkephalin mRNA levels compared to controls. A smaller but consistent increase in dopamine D2 receptor mRNA levels was also found on adjacent sections of the striatum only in animals injected with 150 micrograms of 6-hydroxydopamine. Regional analysis of labeling showed that the increased GAD67, preproenkephalin or dopamine D2 receptor mRNA levels occurred in all striatal sectors examined. Emulsion radioautographs confirmed the increased GAD67, preproenkephalin and dopamine D2 receptor mRNA labeling at cellular level. The present study demonstrates that bilateral 6-hydroxydopamine lesions of dopamine neurons in neonate rats are able to induce a long-term and widespread alteration in the expression of genes encoding for GAD67, preproenkephalin and dopamine D2 receptor in the striatum. In view of previous results after 6-hydroxydopamine lesions in adults, it appears that the behavioral differences observed after adult or neonatal 6-hydroxydopamine lesions are accompanied by a similar alteration of GAD67, preproenkephalin and dopamine D2 receptor gene expression in presumed striatal projection neurons.