A new model of neonatal stress which produces lasting neurobehavioral effects in adult rats.
BACKGROUND
During critical care in neonatal intensive care units (NICU), infants experience stressors and treatments that may produce lasting effects on adult health. An animal model simulating the NICU experience is needed to understand the impact of specific neonatal stressors.


OBJECTIVE
We combined approaches to develop a neonatal rat model simulating NICU stressors in order to examine the hypothesis that early stress and morphine sulfate (MS) exposure would affect development and alter adult behavior.


METHODS
Rat pups were exposed to stressors and given twice daily MS injections (2 mg/kg s.c.) for 5 days (postnatal days 3-7). Stress included daily maternal separation (from 08.00 to 16.00 h), hand feedings, a daily hypoxia/hyperoxia episode (100% N(2) for 8 min, then 100% O(2) for 4 min), and cold exposure (4 degrees C for 20 min/day). Five treatment groups were formed: (1) 'control control' (dam reared and untreated); (2) control vehicle; (3) stress vehicle; (4) control morphine, and (5) stress morphine. Early growth and developmental indices were measured. Adult neurobehavioral tests were paw flick, passive avoidance, and forced swimming. Neonatal MS pharmacokinetics, neonatal and adult corticosterone levels, and adult hematocrit and blood pressure values were measured.


RESULTS
Neonatal stress significantly increased the mortality. Neonatal stress and MS treatment slowed early growth. Neonatal MS impaired passive avoidance learning and increased frequency, duration, and distance of forced swimming. There were no differences in corticosterone, hematocrit, or blood pressure values.


CONCLUSIONS
This model simulates NICU stressors and enables measurement of acute physiological and long-term neurobehavioral indices. Neonatal MS treatment impaired the adult cognitive functioning.
McPherson
Ronald J
RJ
Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, WA 98195-6320, USA.
Gleason
Christine
C
Mascher-Denen
Marcella
M
Chan
Michelle
M
Kellert
Brian
B
Juul
Sandra E
SE
D000701:Analgesics, Opioid / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology; D003080:Cold Temperature / Q000009:adverse effects; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006400:Hematocrit; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007363:Intensive Care Units, Neonatal; D008297:Male; D008426:Maternal Deprivation; D009020:Morphine / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology*
D000701:Analgesics, Opioid; D009020:Morphine; D003345:Corticosterone