Persisting effects on adult brain monoamines of neonatal distress and carbon monoxide exposure

Perinatal factors causing distress or trauma to the neonate are often linked to behavioral abnormalities in development and later life; however, little is known of the long-term effects of these experiences on neurotransmitter systems. This study used carbon monoxide exposure to produce a slow onset and recovery hypoxic episode of two hours in 5-day-old rat pups. This required placement of the pups in a hypothermic environment (air exposure) isolated from the dam so the effects of this distressing experience were also studied. When the brains of these animals were assayed at adulthood, air exposure was found to have increased dopamine and reduced 5-hydroxytryptamine levels in the frontal cortex. Norepinephrine levels were reduced in both midbrain and pons-medulla but the 5-hydroxytryptamine level was increased in midbrain. Hypoxia, induced with carbon monoxide, prevented changes in 5-hydroxytryptamine levels in cortex and brain stem and modified effects on norepinephrine. However, hypoxia resulted in significant decreases in striatal dopamine levels accompanied in females by increased norepinephrine and 5-hydroxytryptamine levels. The data reported here indicate that neonatal distress can have considerable impact on developing neurotransmitter systems. Furthermore, brain region and sex influence the outcome. Carbon monoxide-induced hypoxia, under the same conditions, produced a different pattern of change with particular predeliction for the striatum. Again there were regional and sex differences in the neurotransmitter effects. It is concluded that this hypoxic model may be valuable in the study of developmental disorders.