Classical conditioning of opioid activity in the fetal rat.

Milk promotes activity in the kappa opioid system of the rat fetus that reduces responsiveness to cutaneous stimulation. In this study, fetuses on Gestational Day 20 were presented with an artificial nipple (conditioned stimulus; CS) paired with an intraoral infusion of milk (unconditioned stimulus; US). One paired presentation of the CS and US reduced fetal responsiveness after reexposure to the CS. Selective antagonism of opioid receptors after conditioning indicated that reduced responsiveness was due to mu opioid activity. Mu and kappa opioid activity was evident after 3 paired presentations of CS and US and reexposure to milk. Kappa opioid activity during conditioning was necessary for mu involvement after reexposure to the CS or US. These experiments, which were conducted with fetal subjects that lacked suckling experience, suggest that neurochemical systems engaged during suckling may change rapidly after the newborn's initial experiences at the nipple.