Conditioned opioid activity in the rat fetus.

Abstract

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.

Naloxone attenuation of ethanol-reinforced operant responding in infant rats in a re-exposure paradigm

“…Before being re-exposed to pairings of ethanol and naloxone, animals in the present experiments had experienced ethanol or sucrose reinforcement for two consecutive trials. Opioid activity (specifically, μ-opioid receptors) can be conditioned after pairing a chemosensory CS with a US that promotes the release of endogenous opioids, and subsequently, the animal is capable of exhibiting a conditioned opioid response when the CS is again presented (Arnold et al 1993). So, given that both USs-ethanol and sucrose-are capable of releasing endogenous opioids [unconditioned response], small quantities of these reinforcers acting as a CS may promote a similar conditioned opioid response that is counterconditioned or extinguished by the pairing with naloxone.…”

Increased ethanol intake after prenatal ethanol exposure: Studies with animals

“…These results support the idea of a sensitive period for learning ethanol preferences; a period that probably includes the last prenatal interval also. In fact, as mentioned earlier, it has been observed that during the last days of gestation the fetus can readily acquire chemosensory preferences, and the opioid system is involved in the learning which occurs during this developmental stage (Arnold et al, 1993). In other words, in view of the unique role played by the opioid system during this developmental period (Kehoe, 1988), and bearing in mind that ethanol reinforcing properties are mediated by this neurochemical system (Gianoulakis, 2004) and that ethanol has a low aversive potential for the fetus, it seems plausible that ethanol intoxication may be perceived by the fetus as a positive reinforcer.…”

Fetal Learning About Ethanol and Later Ethanol Responsiveness: Evidence Against “Safe” Amounts of Prenatal Exposure

“…A technique based on the use of a surrogate nipple, applied to the fetus as well as the neonate, has allowed systematic examination of how suckling behavior develops and how early learned experiences modulate subsequent nipple attachment (41). In near-term fetuses (GD 20-GD 21) a single experience comprising access to a surrogate nipple explicitly paired with milk infusions is sufficient to establish conditioned nipple-grasping responses (42,43). The point is to illustrate the rat fetus's capability for learning and memory to which we shall return.…”