Neonatal stress or morphine treatment alters adult mouse conditioned place preference

Hospitalized preterm infants may experience pain and stress, and narcotics are often administered to lessen their suffering. However, prolonged narcotic therapy may be detrimental during neonatal brain development. Using a rat model combining neonatal stress and morphine, we found that neonatal morphine impaired adult learning. Here we describe a new mouse model examining lasting effects of neonatal stress and morphine.

We tested whether repeated neonatal stress and/or morphine exposure affects early neurodevelopmental or adult behaviors.

Five groups of C57/BL6 mice (1: untreated; 2: morphine (2 mg/kg s.c., b.i.d.); 3: saline, 4: stress + morphine; 5: stress + saline) were treated from postnatal day (P) 5 to P9. Stress consisted of daily maternal separation/isolation (08:00-15:00 h) with gavage feedings and twice daily exposure to brief hypoxia/hyperoxia. Developmental behaviors included righting (P5) and negative geotaxis (P9). Adult behaviors included elevated plus maze, morphine place-preference conditioning, and forced-swimming. Plasma concentrations of morphine (P7) and corticosterone (P9 and adult) were measured.

Neonatal stress or neonatal morphine alone impaired adult place-preference conditioning, but the combination did not (interaction p < 0.01). Adult basal corticosterones were reduced by neonatal morphine treatment. There were no substantial differences in elevated plus maze or forced-swimming times.

Neonatal stress and morphine treatment produced long-lasting behavioral and hormonal effects which suggest that neonatal morphine reduces adult arousal and neonatal stress exaggerates adult arousal, each to a degree sufficient to alter learning, while the combined impact of these neonatal treatments does not alter adult learning.