Ontogeny of the dopamine and serotonin transporters in the rat brain: an autoradiographic study.
Damage to monoaminergic systems during the period of brain development is thought to be involved in several neurodevelopmental disorders. We investigated the maturation of the dopamine and serotonin transporters in rat cerebral regions containing the soma and projections of dopaminergic and serotoninergic neurons in an extensive study from the end of embryonic life (E(18)) to adult stages (until P(70)). The membrane transporters were measured by quantitative autoradiography using specific radioprobes. We demonstrated that the dopamine and serotonin transporters have different patterns of development. The dopamine transporter density increased from E(18) to P(28) where it reached the adult level and then remained stable until P(70). The maturation of serotonin transporters followed a triphasic profile in all areas: (i). an increase leading to a peak obtained between P(0) and P(14) in cell bodies and at P(21) in nerve endings; (ii). a decrease to reach adult levels at P(21) in raphe nuclei and at P(28) in projections areas; and (iii). a plateau until P(70). This demonstrated that the last week of embryonic life and the first two postnatal weeks are critical periods in the development of the dopaminergic and serotoninergic systems at which time they could be particularly vulnerable to injury.
Galineau
Laurent
L
Inserm U619, Laboratoire de Biophysique Médicale et Pharmaceutique, Université François Rabelais, Sciences Pharmaceutiques, 31 avenue Monge, 37200 Tours, France.
Kodas
Ercem
E
Guilloteau
Denis
D
Vilar
Marie-Paule
MP
Chalon
Sylvie
S
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography / Q000379:methods*; D001596:Benzylamines / Q000493:pharmacokinetics; D001931:Brain Mapping; D002352:Carrier Proteins / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004622:Embryo, Mammalian; D007554:Isotopes / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009662:Nortropanes / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D050486:Serotonin Plasma Membrane Transport Proteins
D001596:Benzylamines; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007554:Isotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat