Developmental changes in rat brain monoamine metabolism and β-adrenoceptor subtypes after chronic prenatal exposure to propranolol

The aim of this study was to investigate whether a chronic prenatal β-blockade can alter the maturation of the noradrenergic system in the rat brain. Pregnant female and adult male rats were treated for 10 days with the β-antagonist propranolol dissolved in the drinking water (40–50 mg/kg/day). Direct and long-term effects on β-adrenoceptors and monoamine metabolism in various rat brain regions were determined.

After the prenatal treatment the propranolol level in the foetal brain was 0.9 μg/g, while in the adult brain 2.0 μg/g was present. The foetal β1-receptors were significantly up-regulated by propranolol (200%), whereas the β2-receptor number remained unaltered. On postnatal days 4 and 21 the number of both β-subtypes was the same as that of controls. Noradrenaline, its metabolite 3-methoxy-4-hydroxyphenylglycol and their ratio were unaltered directly after the prenatal treatment. In the PN 21 offspring, however, the metabolite level had increased in the frontal cortex (+17%) and hippocampus (+32%), and the ratio in the hippocampus (37%) and medulla pons (+34%). Prenatal treatment also induced a significant increase of the 5-hydroxyindolacetic acid·5-hydroxytryptamine ratio (+15%) in the medulla pons at GD 21. No direct or lasting effects were found on dopamine metabolism. Propranolol treatment of adult rats gave no direct changes in monoamine metabolism.

We concluded that chronic prenatal propranolol exposure (a) reversibly up-regulates foetal β1-adrenoceptors, and (b) increases the NA activity in the brain in later life.