EFFECTS OF IN-UTERO COCAINE EXPOSURE ON THE EXPRESSION OF MESSENGER-RNAS ENCODING THE DOPAMINE TRANSPORTER AND THE D1, D2 AND D5 DOPAMINE-RECEPTOR SUBTYPES IN FETAL RHESUS-MONKEY

The effects of in utero cocaine exposure on the development of the mRN As encoding the dopamine transporter (DAT) and the D1, D2 and D5 dopam ine receptor subtypes were determined in fetal monkey brains at day 45 and day 60 of gestation. Pregnant monkeys were treated with cocaine 3 mg/kg or saline i.m., four times a day from day 18 of gestation until the pregnancy was terminated at day 45 or day 60. The fetal brains we re dissected, and tissue RNA extracted and quantified using ribonuclea se protection assay analysis. In day 45 fetal monkeys, dopamine D1 and D2 receptor subtype mRNAs and DAT mRNA were found in low quantities b oth in control and cocaine-treated subjects. In day 60 fetal monkeys, D1 receptor mRNA levels were highest in the frontal cortex/striatal ar ea, and low to moderate quantities were found in diencephalic and mese ncephalic fetal brain regions. Dopamine D2 receptor mRNA levels were h ighest in the frontal cortex/striatal area, diencephalon and the midbr ain, moderate in the brainstem and low in the caudal temporal lobe and surrounding cortical areas. Dopamine D5 receptor mRNA was expressed i n low quantities throughout the day 60 fetal monkey brain, whereas DAT mRNA was found in the midbrain only. In utero cocaine exposure caused a significant increase in dopamine DI, D2 and D5 receptor subtype mRN As in the frontal cortex/striatal area of day 60 fetal monkeys. These results support the hypothesis that dopamine synthesis and release may be reduced in cocaine-treated fetuses, which results in dopamine rece ptor up-regulation.