Differential regulation of mRNA levels encoding for the two isoforms of glutamate decarboxylase (GAD65 and GAD67) by dopamine receptors in the rat striatum.

Abstract

The effects of in vivo administration of dopamine receptor agonists or antagonists on the mRNA levels encoding for the two isoforms of glutamate decarboxylase, GAD65 and GAD67, and for preproenkephalin were studied in regions of the rat dorsal striatum by radioactive in situ hybridization histochemistry. Changes in striatal mRNA levels after drug treatment were quantified by computerized densitometry on X-ray films. Chronic administration of the dopamine receptor agonist apomorphine or the D1 dopamine receptor agonist SKF-38393 resulted in increased GAD65 mRNA levels in the dorsomedial, ventromedial, dorsolateral and ventrolateral sectors of the striatum. Apomorphine or SKF-38393 treatment did not induce significant effects on GAD67 and preproenkephalin mRNA levels in striatum. On the other hand, chronic administration of the D2 dopamine receptor agonist quinpirole significantly decreased GAD67 in the dorsolateral and ventrolateral and preproenkephalin in the ventrolateral sectors of the striatum. Quinpirole treatment did not induce significant changes in GAD65 mRNA levels. Chronic administration of the dopamine receptor antagonist haloperidol resulted in a significant increase in GAD67 and preproenkephalin mRNA levels in the dorsomedial, dorsolateral and ventrolateral striatal sectors. Chronic treatment with the D2/D3 dopamine receptor antagonist sulpiride resulted in a significant increase in GAD67 in the ventromedial and ventrolateral and PPE in the dorsomedial and ventrolateral striatal sectors. Haloperidol or sulpiride did not induce significant changes in striatal GAD65 mRNA levels. Chronic administration of the D1 dopamine receptor antagonist SCH-23390 had no significant effect on GAD67, GAD65 or preproenkephalin mRNA levels. In the present experimental conditions, stimulation of dopamine receptors with apomorphine or SKF-38393 resulted in increased GAD65 mRNA levels whereas blockade of dopamine receptors with haloperidol or sulpiride resulted in increased GAD67 mRNA levels. These results indicate that striatal GAD65 and GAD67 mRNA levels are differentially regulated by dopamine receptor subtypes.