A preliminary investigation of high retinoic acid exposure during fetal development on behavioral competency and litter characteristics in newborn rats.

Myelomeningocele (MMC) is the most common and severe type of spina bifida in which the developing spine and neural tube fail to close during prenatal development. This typically results in a small portion of the lower spinal cord and meninges protruding from the back of the individual, accompanied by severe motor and sensory deficits. In rats, retinoic acid (RA) exposure in high doses during fetal development has been shown to induce morphologic and clinical symptoms similar to humans with MMC. The aim of the current study was to examine litter characteristics and sensorimotor function in MMC-affected rat pups. Pregnant rats were gavage-fed 2 ml olive oil or all-trans RA (40, 45, 50 mg/kg) on gestational day 11. Pups underwent behavioral testing on postnatal day 2. Litter characteristics and newborn sensorimotor function varied across RA doses. Pups prenatally exposed to 45 and 50 mg/kg RA weighed significantly less than olive oil and 40 mg/kg RA pups. Litters exposed to 45 mg/kg RA suffered significantly higher mortality rates compared to other groups. Additionally, bladder function was significantly impaired in pups exposed to 40 mg/kg RA. Sensorimotor function findings demonstrated that for most behavioral assessments there was not a significant difference between control and RA-exposed subjects. However, pups treated with 40 mg/kg RA showed increased facial wiping, suggesting a hyper-responsiveness to sensory stimuli. Overall, the findings of the current study provide evidence for a model to examine litter characteristics and behavioral effects as well as morphology.

Posture effects on spontaneous limb movements, alternated stepping, and the leg extension response in neonatal rats.

The development of postural control is considered an important factor for the expression of coordinated behavior such as locomotion. In the natural setting of the nest, newborn rat pups adapt their posture to perform behaviors of ecological relevance such as those related to suckling. The current study explores the role of posture in the expression of three behaviors in the newborn rat: spontaneous limb activity, locomotor-like stepping behavior, and the leg extension response (LER). One-day-old rat pups were tested in one of two postures--prone or supine--on each of these behavioral measures. Results showed that pups expressed more spontaneous activity while supine, more stepping while prone, and no differences in LER expression between the two postures. Together these findings show that posture affects the expression of newborn behavior patterns in different ways, and suggest that posture may act as a facilitator or a limiting factor in the expression of different behaviors during early development.

Odor-induced crawling locomotion in the newborn rat: Effects of amniotic fluid and milk.

Early locomotion in the neonatal rat previously has been reported 3 days after birth during exposure to an odor of biological relevance (nest material). The current study explores if other ecologically relevant stimuli-amniotic fluid (AF) and milk-could evoke a similar locomotor response in the newborn rat and whether the endogenous opioid system mediates the response. Newborn rats tested 24 hr after birth were presented with the odors of AF or milk while placed in a runway. Pups expressed crawling and moved along the runway in response to direct exposure to the odors of AF and milk (Exp. 1). However, there was no evidence that this crawling response was altered after pretreatment with the opioid antagonist naloxone (Exp. 2). This study provides evidence of the capacity of AF and milk to evoke coordinated motor behavior, suggesting that they may play a role in the development of fundamental motor patterns.

Opioid mediation of amniotic fluid effects on chemosensory responsiveness in the neonatal rat.

The present study investigated if oral exposure to milk or amniotic fluid (AF) alters responsiveness to sensory stimulation in the neonatal rat, and whether these effects are mediated by the opioid system. Facial wiping evoked by intraoral lemon infusion was used as a measure of sensory responsiveness. Pups were tested in a supine posture, because they showed more paw-face strokes during facial wiping than pups tested prone (Experiment 1). Moreover, pups orally exposed to milk (Experiment 2) or AF (Experiment 3) showed a diminished wiping response to lemon compared to controls exposed to water. Blockade of opioid receptors with the nonselective antagonist naltrexone (Experiment 4) or the kappa antagonist nor-binaltorphimine (Experiment 5) reinstated higher levels of facial wiping after AF exposure. These findings confirm developmental continuity between fetal and neonatal behavioral responses to AF and the ability of AF to induce activity at kappa receptors of the endogenous opioid system.