One of the major concerns in developmental neurobiology is the interrelationship between the growth of presynaptic nerve terminals and the appearance of postsynaptic receptor sites. In this respect contradictory findings on the ontogeny of central nervous system dopaminergic receptors have been reported. Neonatal 6-hydroxydopamine (6-OHDA) denervation apparently caused from an enduring decrease in D2 receptor density (Broaddus and Bennett, 1990) up to D2 receptor supersensitivity (Dewar et al, 1990). D1 receptor development has also been reported either to be independent of postsynaptic DA terminal ingrowth (Dewar et al, 1990) or to be decreased after neonatal 6-OHDA denervation (Gelbard et al, 1990). The current study was undertaken to investigate the effects of selective destruction of dopaminergic neurons during the neonatal phase on the ontogeny of postsynaptic dopamine receptors under standardized conditions in the rat.Pups of inbred Spraque Dawley rats were used in all experiments. On day seven after birth, neonates were pretreated with saline as a control or with desimipramine (20 mg/kg, intraperitoneal) to prevent uptake of 6-OHDA into noradrenergic neurons. One hour later, they received either vehicle as a control or 100 [mu ]g of 6-OHDA intracisternally in 20 [mu ]l of saline. Rats were decapitated at weekly intervals up to 49 days after birth. On each of these occasions the following determinations were done. Scatchard analyses of [ 3 H]SCH23390 binding data (D1 receptor characteristics) and [ 3 H]spiperone binding data (D2 receptor characteristics) were performed on striatal tissue to provide Bmax- and K D values. Dopamine and dopamine metabolite concentrations were determined by a high performance liquid chromatography (HPLC) with electrochemical detection method. Finally the uptake of [ 3 H]dopamine into crude synaptosomes prepared from striatal tissue was measured.The results of the [ 3 H]dopamine uptake studies showed that the extent of the destruction of presynaptic terminals was approximately 60%. Neither the K D nor the Bmax of [ 3 H]SCH23390 binding to D1 receptors showed statistically significant differences from control values in the neonatally 6-OHDA denervated striatal tissue. A small but not statistically significant lowering of [ 3 H]SCH23390 binding was observed at 42 days of age. No differences in the Bmax or K D values for [ 3 H]spiperone binding between 6-OHDA treated and control rats were observed at any of the ages examined. Dopamine content in the striatum was lowered at all ages examined. Maximal depletion occurred at day 42 after birth. Similar lowerings of DA metabolites (DOPAC and HVA) were measured.The results suggest that striatal D1 and D2 dopamine receptors develop independently of postsynaptic dopaminergic terminal ingrowth.