| 20211707 |
Slotkin TA, Seidler FJ: Mimicking maternal smoking and pharmacotherapy of preterm labor: Interactions of fetal nicotine and dexamethasone on serotonin and dopamine synaptic function in adolescence and adulthood. Brain Res Bull. 2010 Mar 6.
Fetal coexposure to nicotine and dexamethasone is common: maternal smoking increases the incidence of preterm delivery and glucocorticoids are the consensus treatment for prematurity. We gave pregnant rats 3mg/kg/day of nicotine throughout gestation, a regimen that reproduces smokers' plasma levels, and then on gestational days 17, 18 and 19, we administered 0.2mg/kg of dexamethasone. We evaluated developmental indices for serotonin (5HT) and dopamine synaptic function throughout adolescence, young adulthood and later adulthood, assessing the brain regions possessing major 5HT and dopamine projections and cell bodies. Males displayed persistent upregulation of 5HT (1A) and 5HT (2) receptors and the 5HT transporter, with a distinct hierarchy of effects: nicotine receptor with the same rank order; both sexes displayed presynaptic hyperactivity of 5HT and dopamine pathways as evidenced by increased neurotransmitter turnover. Superimposed on these overall effects, there were significant differences in temporal and regional relationships among the different treatments, often involving effects that emerged later in life, after a period of apparent normality. This indicates that nicotine and dexamethasone do not simply produce an initial neuronal injury that persists throughout the lifespan but rather, they alter the developmental trajectory of synaptic function. The fact that the combined treatment produced greater effects for many parameters points to potentially worse neurobehavioral outcomes after pharmacotherapy of preterm labor in the offspring of smokers. |
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