Contrasting Effects of Raclopride and SCH 23390 on the Cellular Content of Preproenkephalin A mRNA in Rat Striatum: A Quantitative Non‐radioactive In Situ Hybridization Study

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Abstract
The effects of acute i.p. administration of selective dopamine (DA) receptor antagonists on the expression of preproenkephalin A (PPE A) mRNA was investigated in the adult rat striatum. Animals were injected with either (a) a selective D1 receptor antagonist SCH 23390 (0.25 mg/kg), (b) a selective D2 receptor antagonist raclopride (5 mg/kg), or (c) SCH 23388 (0.25 mg/kg), the (S)-enantiomer of SCH 23390. Control naive animals did not receive an injection. At specific time points following drug administration (1, 3 or 9 h), rats were killed and striatal tissue processed for in situ hybridization with an alkaline phosphatase-labelled oligonucleotide probe complementary to a portion of the rat PPE A cDNA. Treatment of rats with SCH 23388 did not affect the content of PPE A mRNA expressed by striatal cells at any time point. However, 1 h after SCH 23390 administration, a significant decrease in striatal PPE A mRNA was detected, reflected by a decrease in the cellular content of mRNA. No significant changes in PPE A mRNA were detected in raclopride-treated sections at this time point. In contrast, both 3 and 9 h after an injection of raclopride a significant increase in the cellular content of PPE A mRNA was detected in the striatum. No change in the cellular content of mRNA was detected in SCH 23390-treated rats at these two latter time points. Throughout the striatum approximately 46% of neurons were found to express PPE A mRNA, with the highest percentage of cells (55%) being detected in the mid-caudal striatum. No significant differences in striatal DA content were detected with any drug treatment using HPLC electrochemical detection methods. These results demonstrate that acute administration of the DA D1 and D2 receptor antagonists has contrasting effects on the cellular content of PPE A mRNA in the adult rat striatum. These effects may reflect changes in the rate of mRNA transcription which may be mediated by cAMP.