Classical conditioning in the rat fetus: Involvement of mu and kappa opioid systems in the conditioned response

Abstract

When the Embryonic Day 20 (E20) rat fetus is given a conditioning trial involving a paired presentation of an artificial nipple (the conditioned stimulus; CS) with an intraoral infusion of milk (the unconditioned stimulus; US), it shows evidence of classical conditioning when again exposed to the CS during a test trial. Specifically, the fetus shows fewer oral grasp responses (the conditioned response; CR) when continuously presented with the artificial nipple. The present study further investigated this classically conditioned reduction in oral grasping. Separate experiments (a) examined the time course of the reduction in oral grasping (Experiment 1), (b) characterized the time course of mu opioid (Experiment 2) and kappa opioid (Experiment 3) involvement in the CR, and (c) described changes in fetal behavior (Experiment 4) associated with mu and kappa opioid effects on responding to the artificial nipple. The results are discussed in terms of opioid involvement in establishing and maintaining early suckling behavior.

Classical conditioning in the rat fetus. III. Retention, extinction, and re‐activation of the conditioned response (CR)

“…Classical conditioned fetuses show fewer oral grasp responses, compared to control fetuses, during a test trial when they are re-exposed to the artificial nipple (CS). These findings replicate earlier reports of one-trial classical conditioning in the E20 rat fetus involving formation of an association between stimuli normally present immediately after birth in the context of suckling (Petrov et al, 2000;Robinson & Smotherman, 1997;Smotherman, 2002b).…”

“…When reexposed to the artificial nipple CS after conditioning and observed in the test of oral grasping, fetuses show fewer oral grasp responses compared to control fetuses exposed to the milk (US) and artificial nipple (CS) in an unpaired fashion. These findings replicate earlier reports of one-trial classical conditioning in the E20 rat fetus (Petrov, Varlinskaya, & Smotherman, 2000;Robinson & Smotherman, 1997;Smotherman, 2002b). The classically conditioned reduction in oral grasping is evident when the test of oral grasping is administered 18 min after conditioning, but not when it is administered 21 to 30 min after conditioning (Experiments 1a and 1b).…”

Changing Mechanisms of Opiate Tolerance and Withdrawal during Early Development: Animal Models of the Human Experience

“…It is not known whether withdrawal induces a negative affective state in the fetus (Handelsman et al 1992; Kanof et al 1993). If so, the fetus, which can learn in utero (e.g., DeCasper and Fifer 1980; Smotherman 2002; Stickrod et al 1982; for review, Moon and Fifer 2000), could associate maternal cues (e.g., odors) with that aversive state. That association might affect later attachment to the mother, although to our knowledge there are no data that bear on this speculation.…”

Fetal learning: a critical review

“…Also, these studies have largely focused on the human fetus rather than animal models. In contrast, virtually all the classical conditioning research into fetal learning has been in animal models using taste and/or smell as the stimulus Feijoo, 1981;Pavlov, 1906;Smotherman, 1982;2002a, 2002bSmotherman & Robinson, 1985Spelt, 1948;Varlinskaya, Petrov, Simonik, & Smotherman, 1997). Most of the work in this area, however, has used exposure learning as the model and has also used the widest variety of stimuli (vibro-acoustic, smell/taste and movement) (Abate, Pepino, Spear, & Molina, 2004;Chotro & Molina, 1992;Damstra-Wijmenga, 1991;DeCasper & Fifer, 1980;DeCasper & Spence, 1986;Fifer & Moon, 1989;Hepper, 1988Hepper, , 1991Hepper, Scott, & Shahidullah, 1993;James, Spencer, & Stepsis, 2002;Mennella, Jagnow, & Beauchamp, 2001;Moon & Fifer, 2000;Nelson, Brightwell, MacKenzie-Taylor, Burg, & Massari, 1988;Robinson, 2005;Shetler, 1989).…”