Postnatal development of presynaptic alpha-adrenoceptors in rat cerebral cortex: studies with brain slices and synaptosomes.

The development of alpha-adrenoceptor mediated presynaptic modulation of noradrenaline (NA) release in the rat cerebral cortex was studied during the first postnatal month by examining the effects of exogenous NA and phentolamine in K+-induced [3H]NA release from superfused slices or synaptosomes. Exogenous NA strongly inhibited [3H]NA release from cortex slices of newborn rats, indicating that presynaptic alpha-receptors exist already on the day of birth. In fact, at least up to and including the 17th day after birth, Na caused a stronger inhibition of [3H]NA release from neonatal than from adult cortex slices. However, with synaptosomal preparations the inhibitory effect of NA was found to be similar in neonatal and adult rats. Further analysis of the data obtained with brain slices suggested that the differences between neonatal and adult rats observed with regard to the presynaptic modulation of [3H]NA release could be ascribed to differences in the concentrations of released endogenous NA in the extracellular spaces of brain slices. This hypothesis was strengthened by the data obtained in experiments using cortex slices of adult rats in which the endogenous NA level was lowered by pretreatment with alpha-methylparatyrosine. In cortex slices of neonatal (7-day-old) rats the concentration of endogenous NA released upon stimulation with 26 mM K+ in the vicinity of presynaptic alpha-receptors was estimated to be about 10 nM, as compared to approximately 25 nM in adult cortex slices. In both cases NA (i.e. exogenous + endogenous) appeared to cause maximally about 80% inhibition of [3H]NA release from cortex slices.