Classical conditioning in the fetal rat with a long delay between presentation of CS and US.

A single paired presentation of the artificial nipple and milk results in classical conditioning of changes in perioral responsiveness in the E20 rat fetus. This classical conditioning is evidenced by a reduction in responding to perioral tactile stimulation. The results of Experiment 1 confirmed the specificity of milk as an unconditioned stimulus to support classical conditioning. Experiment 2 demonstrated that single-trial classical conditioning with the artificial nipple CS and milk US was possible with a delay of 30 s between nipple and milk presentations. Further, measurements of fetal motor behavior during the delay between CS and US presentations indicated that a single 15-s presentation of the artificial nipple increased movements of the mouth for 30 s after removal of the artificial nipple. Experiment 3 demonstrated that three exposures to the artificial nipple prolonged the expression of mouthing for up to 120 s and made possible single trial classical conditioning with a delay of 120 s between CS and US presentations. The capacity of the fetal CNS to maintain a "behavioral trace" for an ecologically important stimulus, such as the nipple, could have adaptive significance in the early development of motivated behavior.

Central administration of cocaine produces age-dependent effects on behavior in the fetal rat.

Rat fetuses were exposed to cocaine, lidocaine, or saline on Gestational Day 20 or 21 to provide information about cocaine effects on behavior during prenatal development. Cocaine was administered into the cisterna magna of individual fetal subjects to restrict effects to the CNS. Behavioral effects of cocaine were compared with lidocaine to help distinguish the effects of cocaine on monoamine systems in the brain from its properties as a local anesthetic. Cocaine promoted 3-5-fold increases in fetal motor activity in the absence of explicit sensory stimulation, in contrast to the slight suppressive effects of lidocaine. Cocaine and lidocaine also reduced coordinated behavioral responses to an artificial nipple. The behavioral effects of cocaine administered into the CNS of fetal subjects suggest specific mechanisms of action on developing neural and behavioral systems in the late prenatal period.

Cocaine alters cyclic motor activity in the fetal rat.

Individual rat fetuses were exposed to cocaine by injection into the cisterna magna on E20 or E21 of gestation. On E20, cocaine elevated motor activity throughout the 20-min session, with activity increasing to double SAL-injected levels by the end of the session. On E21, overall activity also was elevated after cocaine, increasing four- to fivefold in the first 5 min of the session, and decreasing to twice the levels of SAL controls thereafter. Movement time series were subjected to spectral analysis to characterize cyclic motor organization. Cyclicity was evident in 67% of control and 97% of cocaine-injected fetuses. Cocaine increased the number of peaks in the movement spectrum and resulted in greater spectral density at the primary frequency of cyclic movement. Prenatal exposure to cocaine may alter patterns of cyclicity in the fetus, with consequences for the normal development of attention and behavioral state in the neonate.

Cocaine alters behavior in the rat fetus.

Changes in motor behavior and sensory responsiveness were characterized in rat fetuses on gestational Day 21 after acute administration of various doses of cocaine. An increase in fetal motor activity was evident in the 3 highest doses (5, 10, and 20 mg/kg). Cocaine-exposed Ss showed reduced facial wiping in behavioral bioassays of cutaneous sensitivity (10 and 20 mg/kg) and chemosensory responsiveness (20 mg/kg). Changes in other behavioral measures indicated that fetuses detected and responded to these stimuli, suggesting that reduced facial wiping was due to a disruption of sensorimotor integration or motor coordination. Study of the fetus in vivo can provide insights into the mechanisms of cocaine's deleterious effects on central nervous system and behavioral development.

Mu and kappa opioid systems modulate responses to cutaneous perioral stimulation in the fetal rat.

The prenatal ontogeny of functional mu and kappa opioid systems was investigated in a series of four experiments conducted with rat fetuses on the last day of gestation (E21). Fetal motor activity and responsiveness to cutaneous stimulation were measured following administration of various opioid agonists, including morphine, DAMGO, U69,593, and U50,488. The effectiveness of selective mu (CTOP) and kappa (nor-binaltorphimine) antagonists to block the effects of opioid agonists, and the effects of combined administration of DAMGO and U69,593, also were assessed. These experiments provide evidence that both mu and kappa opioid systems are functional and are capable of modulating fetal behavior during the late prenatal period. The data also suggest that different subclasses of kappa receptors may mediate different aspects of fetal behavior. These findings suggest a role for endogenous opioids in regulating important aspects of perinatal behavior, including the development of suckling, maternal-infant interaction and early learning at the nipple.