Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: contrasting effects of D1 and D2 antagonists

Abstract

In situ hybridization was used to measure the levels of proenkephalin mRNA and prodynorphin mRNA in regions of rat striatum and nucleus accumbens. Chronic administration of haloperidol (2.4 mg/kg/day for 7 days) increased the levels of proenkephalin mRNA in both striatum and nucleus accumbens. In contrast, the levels of prodynorphin mRNA were not significantly affected in any region. Chronic administration of the D1 antagonist SCH 23390 (2.4 mg/kg/day for 7 days) decreased the striatal content of proenkephalin mRNA. A similar effect was seen in the lateral nucleus accumbens. The levels of prodynorphin mRNA were unaffected by SCH 23390 treatment in all regions examined. These results suggest that there is no major tonic dopaminergic regulation of prodynorphin synthesis in the basal ganglia. However, it appears that there is a tonic suppression, via D2 receptors, and a tonic enhancement, via D1 receptors, of proenkephalin synthesis, in the striatum and nucleus accumbens.