Effects of neonatal 6-hydroxydopamine injections on glutamate decarboxylase, preproenkephalin and dopamine D 2 receptor mRNAs in the adult rat striatum

Abstract

The effects of neonatal 6-hydroxydopamine injections on the levels and cellular distribution of glutamate decarboxylase (GAD67), preproenkephalin and dopamine D 2 receptor messenger RNAs were studied in the striatum of adult rats. Cerebroventricular injections of 150 μg or 100 μg 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 D 2 receptor mRNA levels was also found on adjacent sections of the striatum only in animals injected with 150 μg of 6-hydroxydopamine. Regional analysis of labeling showed that the increased GAD67, preproenkephalin or dopamine D 2 receptor mRNA levels occured in all striatal sectors examined. Emulsion radioautographs confirmed the increased GAD67, preproenkephalin and dopamine D 2 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 D 2 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 D 2 receptor gene expression in presumed striatal projection neurons.