This project evaluates the infant neurobehavioral function after administration of opiate analgesics during labor. We have established a nonhuman primate model (rhesus monkey) for labor, delivery and infant assessment. Neurobehavioral assessments of infants exposed to meperidine (2 mg/kg) via treatment of the dam during labor have been completed through 14 weeks of age. The proposed research provides follow up of meperidine exposed monkey infants to 12 months of age, a developmental period approximately equivalent to the preschool child. Follow-up tests have been selected on the basis of preliminary results suggesting that regulation of activity and attention may be affected by the drug. In addition, consideration of the impact of exogenous opiate agents will be extended to the """"""""at risk"""""""" newborn in experiments combining meperidine treatment with mild neonatal hypoxia. Finally, the role of the endogenous opiate system in modifying neurobehavioral development will also be studied by introducing opiate receptor blockade during labor. It should be emphasized that all procedures are designed to be within the range of human obstetric and pediatric practice and that no destructive procedures or animal sacrifice are involved. The goal of obstetric analgesia is to provide maternal pain relief with minimal adverse fetal consequences. Opiate analgesics, and in particular meperidine, are widely used because of ease of administration, and extensive clinical experience in the obstetric situation. Further they possess a unique and effective analgesic potency which we now know is related to their interaction with the endogenous opiate system. As more becomes understood of the endogenous opiate system, the mechanism of pain relief and the role of the system in prenatal and early postnatal life, this information can be exploited in devising safer and more effective use of opiate agents in obstetrics. Thus in addition to continuing the evaluation of exogenous opiate agents the present proposal also includes an investigation of the role of the endogenous opiate system through treatment with the opiate blocker naloxone in the obstetric situation. The particular focus of this comparison is neurobehavioral function in infancy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM032920-03
Application #
3282144
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-01-01
Project End
1988-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Golub, M S; Germann, S L (1998) Perinatal bupivacaine and infant behavior in rhesus monkeys. Neurotoxicol Teratol 20:29-41
Golub, M S; Kaaekuahiwi, M A; Eisele, P H et al. (1998) Newborn tissue concentrations of bupivacaine following maternal epidural administration during labor in guinea pigs. Biol Neonate 74:304-13
Golub, M S (1996) Labor analgesia and infant brain development. Pharmacol Biochem Behav 55:619-28
Golub, M S; Donald, J M (1995) Effect of intrapartum meperidine on behavior of 3- to 12-month-old infant rhesus monkeys. Biol Neonate 67:140-8
Golub, M S; Kaaekuahiwi, M A (1995) Response to maternal separation in infant guinea pigs exposed to intrapartum meperidine. Dev Psychobiol 28:59-68
DeWeert, T M; Golub, M S; Kaaekuahiwi, M A (1995) Long-term epidural catheterization of rhesus macaques: loss of resistance technique. Lab Anim Sci 45:94-7
Eisele, P H; Kaaekuahiwi, M A; Canfield, D R et al. (1994) Epidural catheter placement for testing of obstetrical analgesics in female guinea pigs. Lab Anim Sci 44:486-90
Golub, M S; Eisele Jr, J H; Donald, J M (1991) Effect of intrapartum meperidine on the behavioral consequences of neonatal oxygen deprivation in rhesus monkey infants. Dev Pharmacol Ther 16:231-40
Golub, M S (1990) Use of monkey neonatal neurobehavioral test batteries in safety testing protocols. Neurotoxicol Teratol 12:537-41
Golub, M S; Eisele Jr, J H; Hwang, F Y et al. (1989) Late-pregnancy changes in peripheral plasma beta-endorphin in rhesus monkeys (Macaca mulatta). Gynecol Obstet Invest 27:113-7

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