ABSTRACT
Most studying the consequences of prenatal cocaine (COC) exposure employ rodents or other multiparous organisms in their models. We have previously shown that when pregnant Sprague-Dawley albino rats are administered a 30 mg/kg subcutaneous (s.c.) injection on embryonic day 15 (E15), fetal brain COC levels show a proximal-to-distal (in relation to the cervix) gradient that can vary by as much as 350%. The present study sought to determine whether this gradient translated into a similar gradient in brain dopamine (DA) levels. Pregnant rats were administered COC or saline (SAL) (30 mg/kg COC or 1 ml/kg SAL, b.i.d., E7-E19). On E20, dams were anesthetized with halothane, the fetuses immediately removed, their brains excised, frozen and subsequently processed for DA, dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA). High-performance liquid chromatography (HPLC) analysis revealed a proximal-to-distal gradient for DA in both COC- and SAL-exposed fetuses. Average fetal DA levels per litter were significantly lower in COC-exposed litters (57.39 ± 3.67 ng/hemibrain SAL; 48.29 ± 3.87 ng/hemibrain COC F7,1 = 11.66, p <0.05). The gradients for DA were in opposite directions such that COC litters showed the lowest levels of DA in the most distal uterine positions, whereas SAL-exposed litters showed the highest DA levels in the same location. These data suggest that a gradient in brain dopamine normally exists for fetuses based upon uterine position, and that cocaine can have selectively greater effects on this level as a function of fetal location.
