Distribution of α2-Adrenergic Receptor Binding in the Developing Human Brain Stem

Rapid and dramatic changes occur in cardiorespiratory function during early human life. Catecholamines within select brain stem nuclei are implicated in the control of autonomic and respiratory function, including in the nucleus of the solitary tract and the dorsal motor nucleus of X. Animal and adult human studies have shown high binding to α2-adrenergic receptors in these regions. To determine the developmental profile of brainstem α2-adrenergic binding across early human life, we studied brain stems from five fetuses at mid-gestation, three newborns (37–38 postconceptional weeks), and six infants (44–61 postconceptional weeks). We used quantitative tissue receptor autoradiography with [3H]para-aminoclonidine as the radioligand and phentolamine as the displacer. In the fetal group, binding was high (63–93 fmol/mg tissue) in the nucleus of the solitary tract, dorsal motor nucleus of X, locus coeruleus, and reticular formation; it was low (<32 fmol/mg tissue) in the principal inferior olive and basis pontis. Binding decreased in all regions with age: in infancy, the highest binding was in the intermediate range (32–62 fmol/mg tissue) and was localized to the nucleus of the solitary tract and dorsal motor nucleus of X. The most substantial decrease in binding (75%–85%) between the fetal and infant periods occurred in the pontine and medullary reticular formation and hypoglossal nucleus. Binding remained low in the principal inferior olive and basis pontis. The decreases in binding with age remained significant after quench correction. These data suggest that rapid and dramatic changes occur in early human life in the brain stem catecholaminergic system in regions related to cardiorespiratory control.