[Functional development of the synaptic transmission in the rat CNS and its interaction with drugs (author's transl)]

The ontogenesis of the synaptic function was investigated in the central noradrenaline (NA), dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and GABA nervous systems of developing rats. Monoamines histochemically first appeared on days 12 to 14 in the fetal brain and may exert a trophic action on target neurons as a "differentiation signal". The presynaptic functions such as the high affinity uptake and depolarization-induced, Ca2+-dependent release of L-[3H]DA, and [2H]DA, and [3H]DA, and [3H]5-HT were observed in synaptosomes and slices from the fetus (18 days of gestation) and brain of newborn rats. Monoamine-stimulated activity of adenylate cyclase and specific binding of ligands in NA(alpha 1, alpha 2, beta 1, beta 2), DA, 5-HT, ACh (muscarinic and nicotinic) and GABA receptors indicated dynamic changes through postnatal development. Behavioral findings suggest when neurotransmitter receptors become sensitive and reach functional maturity (NA and DA, already at birth; 5-HT and muscarinic ACh, 15 to 20 days; GABA, 12 to 13 days (mouse)). In addition, differences in behavioral responsiveness to drugs were observed in rats at various developing stages, probably due to the interaction between plural neuronal systems. Finally, the brain undergoing rapid differentiation seems to be most sensitive to hormones and centrally acting drugs. Thus, permanent alteration in central functions may occur when some classes of drugs, dose-dependently, are administrated to animals at the perinatal stage.