Reserpine treatment stimulates enkephalin and D2 dopamine receptor gene expression in the rat striatum

We investigated the effect of catecholamine depletion on gene expression for preproenkephalin A (PPA) and D2 dopamine receptor (D2R) in the rat nigrostriatal complex, using quantitative Northern blot analysis. The D2R probe indifferently recognizes the two mRNA isoforms generated by alternative splicing from the same gene. Short-term and chronic reserpine treatment increase the level of PPA and D2R mRNA in the striatum in a complex manner. For short-term treatment, we injected 10 mg/kg of reserpine the first day, 5 mg/kg 24 h later and sacrificed the rats at various times after the last injection. This treatment resulted in an increase of the level of PPA mRNA by 50% and D2R mRNA up to 150%. For chronic treatment, we injected 0.5 mg/kg of reserpine for 21 days, sacrificed the rats one day after the last injection and observed an increase in PPA and D2R mRNA levels by 100%. Statistical analysis revealed that the PPA mRNA level after chronic treatment was significantly higher from the one obtained after short-term treatment while no such difference was observed for the D2R mRNA. In contrast, reserpine treatment does not modify the level of D2R mRNA in the substantia nigra suggesting that catecholamine depletion has postsynaptic but not presynaptic consequences in the rat nigrostriatal complex. These results demonstrate that reserpine acts at the gene or the mRNA level to induce dopamine supersensitivity in striatal dopaminoceptive neurons.