Postnatal development of the dopamine transporter: A quantitative autoradiographic study

The dopamine transporter performs an important role in regulating neurochemical transmission at dopaminergic synapses, as well as dopamine synthetic activity in dopaminergic neurons. Certain drugs and toxins exert effects at the transporter, especially cocaine, a common drug of abuse. We studied the development of these sites in the rat at postnatal ages day 0, 5, 10, 15, 21 and adult using quantitative autoradiography with the cocaine analogue [I-125]RTI-55. At birth, certain structures such as the substantia nigra, interstitial nucleus of the medial longitudinal fasciculus, frontal and parietal cortex, and substantia inominata had [I-125]RTI-55 binding levels that were already near the adult value. The striatum developed later, showing earlier growth in the anterior and dorsolateral regions, with early localization in both striosomes and a subcallosal streak. Anterior-to-posterior and lateral-to-medial gradients were present at day 0. The anterior striatum, ventral tegmental region, substantia nigra compacta and bed nucleus of the stria terminalis showed transient peaks in binding levels that were higher than the adult values. Structures showing relatively late development included the prefrontal cortex, nucleus accumbens shell, olfactory tubercle and subthalamic nucleus. Knowledge of the differential development patterns of the dopamine transporter in different brain regions may have implications for understanding the neurodevelopmental effects of prenatal cocaine exposure.