A transient expression of functional alpha2-adrenergic receptors in white matter of the developing brain

Norepinephrine is a neurotransmitter with peripheral and central actions mediated by alpha-1, alpha-2, and beta-adrenergic receptors. In this paper, we report an expression of alpha-2 adrenergic receptors in developing white matter tracts as revealed by [(3)H]RX821002 autoradiography. In rats, these receptors are present in the corpus callosum and anterior commissure at gestational day 20. Quantification of their postnatal expression reveals peak expression in the corpus callosum at postnatal day 1, which decreases with maturation and disappears by postnatal day 21. Expression in the anterior commissure is persistently elevated throughout the first ten days of postnatal development and then decreases to near background levels by postnatal day 21. Further characterization of the receptors by agonist-stimulated [(35)S]GTPgammaS binding verifies alpha-2 adrenergic receptors are functionally coupled to G proteins early in development and therefore are mature receptors. In situ hybridization did not detect mRNA for any of the alpha-2 adrenergic receptor subtypes (A, B, and C) in white matter tracts of postnatal day 5 brain. [(3)H]RX821002 emulsion autoradiography demonstrated autoradiographic grains that were of comparable density between cells and over cell bodies. Collectively, these data suggest that alpha-2 adrenergic receptors in neonatal commissures are synthesized at sites distant from their white matter expression and may be guiding the maturation of these brain commissures.