Fetal behavior and the endogenous opioid system: D1 dopamine receptor interactions with the kappa opioid system

Opioid or dopaminergic drugs can alter the motor behavior of rat fetuses on day 21 of gestation (E21). This study was conducted to a) characterize the behavioral effects of specific opioid agonists in the fetus, b) determine the effects of selective blockade of opioid receptors, and c) characterize the interaction between the dopamine and kappa opioid systems. Neither morphine nor the mu agonist DAMGO produced effects on fetal motor activity, whereas the kappa agonist U50,488 resulted in a pronounced increase in motor behavior. The selective antagonists beta-funaltrexamine (mu) and nor-binaltorphimine (kappa) produced no behavioral effects when administered alone. The D1 antagonist SCH-23390 did not reverse the activational effects produced by U50,488, but the kappa antagonist nor-binaltorphimine successfully blocked the increases in fetal behavior produced by the D1 agonist SKF-38393. These results are consistent with the hypothesis that activation of the dopamine system promotes activity at kappa opioid receptors to bring about changes in fetal motor activity.