Plasticity and ontogeny of the central 5-HT transporter: effect of neonatal 5,7-dihydroxytryptamine lesions in the rat.

5,7-Dihydroxytryptamine (5,7-DHT) is unique as a serotonin (5-HT) neurotoxin in that i.p. injection of neonatal rats increases concentrations of 5-HT in brainstem while depleting 5-HT in cortex, hippocampus and spinal cord. To study the mechanism of this effect we measured the 5-HT transporter or uptake site, a presynaptic marker, using [3H]paroxetine binding. There were significant regional differences in Bmax of vehicle-injected rats: brainstem, diencephalon > striatum, cortex, spinal cord > hippocampus, cerebellum. There were also regional differences in the ontogeny of bindings sites: at postnatal day 7, [3H]paroxetine sites were 39% of adult levels in cortex compared to 63% in brainstem. Thirty days after 100 mg/kg 5,7-DHT i.p., Bmax of [3H]paroxetine binding was significantly increased in brainstem (+67%) and diencephalon (+136%), whereas it decreased in cortex (-59%), hippocampus (-94%) and spinal cord (-99%), striatum (-41%) and cerebellum (-37%). KD remained unaltered. In dose-response studies (0-200 mg/kg), 50 mg/kg was the threshold dose for Bmax effects and 200 mg/kg was lethal. In weekly time-course studies, changes were apparent 1 week after 5,7-DHT lesions. Binding site increases in diencephalon and brainstem were not maximal until 3 weeks after injection, whereas percent decreases in cortical sites remained unchanged at each week studied. Lesion effects on the ontogeny of [3H]paroxetine binding sites were region-dependent: cortical sites continued to increase with age but spinal sites did not. There was no significant recovery in spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)