It has been reported from this laboratory that prenatal cocaine exposure results in the postnatal transient alterations of rat striatal dopamine uptake sites examined from postnatal 0-32 wk. The present study aims to examine whether this will result in a direct/indirect stimulation of dopamine D2 receptors. Pregnant rats were dosed orally with cocaine hydrochloride (60 mg/kg/d) from gestational day (GD) 7-21. Control animals received an equivalent volume of water. The striatum from the offspring at postnatal 0-32 wk was examined. The radioligand [3H]sulpiride was used for the Scatchard analysis of the D2 receptors, and the changes in the levels of mRNA for the D2 receptor were studied using Northern blot analysis. Results from the present study revealed that in the control group, there was an age-dependent increase in the number of D2 receptor sites (Bmax:44.00±2.12 to 178.00±45.10 fmol/mg protein) and in the levels of D2 mRNA from PN0-32 wk with the most rapid increase occurring during the first 4 wk of postnatal development. Prenatal cocaine exposure resulted in only a significant decrease (p<0.001) in the number of D2 receptor sites at PN0 wk and in a 10% increase in mRNA levels at PN3, 4, and 12 wk. It was concluded from this study that prenatal cocaine exposure resulted in minimal postnatal changes in the dopamine D2 receptor. © 1995 Humana Press Inc.