Fetal behavior and the dopamine system: activity effects of D1 and D2 receptor manipulations

Binding studies have indicated that D1 and D2 dopamine receptor subtypes are present in rats before birth, but it is not known whether these receptors are functional during the prenatal period. In the present study, day-21 rat fetuses were prepared for direct observation after pharmacological manipulation of D1 and/or D2 receptors. The D1 agonist SK&F38393 induced a marked increase in fetal activity (i.e., forelimb, rearlimb, and head movements) while the D2 agonist quinpirole produced a slight suppression in activity. Coadministration of both agonists resulted in low levels of fetal activity, suggesting an interaction between D1 and D2 receptors. Administration of the D2 antagonist sulpiride resulted in little change in fetal behavior but was effective in blocking the behavioral activation induced by the D1 agonist. The D1 antagonist SCH23390, administered alone or in combination with the D2 antagonist, produced a modest increase in fetal activity that included mouthing and facial wiping behavior. These data provide evidence that the dopamine system is functional and capable of mediating behavioral effects in the near-term rat fetus. Further, manipulation of dopamine receptors results in a different pattern of behavioral effects than has been reported in older animals. The observation that fetal behavior is influenced by these pharmacological challenges suggests that drugs of abuse known to affect the dopamine system, such as cocaine, may cause profound changes in fetal behavior in utero that could consequently lead to alterations in behavioral and CNS development.