Conditioned opioid activity in the rat fetus.

Classical conditioning in the rat fetus (Embryonic Day 20) was investigated in 4 experiments. Reexposure to a conditioned stimulus (CS; sucrose), after 3 pairings with an unconditioned stimulus (US; milk), reduced fetal facial wiping in a bioassay of perioral cutaneous responsiveness. Reduced responsiveness was evident only in subjects that received paired presentations of the CS and US and cannot be attributed to habituation, sensitization to the CS, or protracted effects of US exposure during conditioning trials. Fetuses attended to the chemosensory, not the tactile, qualities of the sucrose infusion during CS reexposure. Changes in fetal responsiveness resulted from conditioned activity in the endogenous opioid system, specifically at mu opioid receptors. These data confirm that the rat fetus is capable of exhibiting a conditioned opioid response in utero.