Regulation of D1A and D2 dopamine receptor mRNA during ontogenesis, lesion and chronic antagonist treatment.

The developmental characteristics of D1A and D2 dopamine receptor mRNA levels were determined by Northern blot analyses. Striatal D1A and D2 dopamine receptor mRNAs of male Fischer 344 rats were about 60% of adult (day 120) levels at postnatal day 1 and reached their highest levels at day 30 (126 and 139% adult levels) and then decreased by day 120 (100%). D1 and D2 dopamine receptors showed much greater quantitative changes with densities at day 30 about 6- and 14-fold higher than at day 1, respectively, while mRNA levels showed only a 2-fold increase. The highest level of D2 dopamine receptor mRNA in the midbrain was reached at day 14 (195% of adult levels) while the level at day 1 was 31% higher than that at day 120. Striatal beta-actin mRNA levels decreased gradually as the rats developed with the level at postnatal day 1 almost twice that at day 120 postpartum. Treatment of adult rats with the selective D2 dopamine receptor antagonist, haloperidol (0.5 mg/kg/day, s.c., for 2 h, 7, 14, 21 days or 21 days + 3 days withdrawal) had no effect on striatal D2 dopamine receptor mRNA levels in spite of significant increases in dopamine receptor density at the later time points. However, 21 days following a 6-hydroxydopamine lesion of the nigrostriatal pathway, striatal D2 dopamine receptor mRNA levels were increased by 53%.