PharmacologyBiochemistry & Behavior, Vol. 37, pp. 371-373. ©Pergamon Press plc, 1990. Printed in the U.S.A. 0091-3057/90$3.00 + .00 RAPID COMMUNICATION Weanling Rats Exposed Prenatally to Cocaine Exhibit an Increase in Striatal D2 Dopamine Binding Associated With an Increase in Ligand Affinity F. M. SCALZO,*t S. F. ALl,* N. A. FRAMBES:~ AND L. P. SPEAR:~ *Division of Reproductive and Developmental Toxicology, HFT 130 National Center for Toxicological Research, Jefferson, AR 72079 "pDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205 $Center for Developmental Psychobiology, Department of Psychology State University of New York at Binghamton, Binghamton, NY 13910 Received 28 June 1990 SCALZO, F. M., S. F. ALl, N. A. FRAMBES AND L. P. SPEAR. Weanlingrats exposed prenatally to cocaine exhibit an increase in striatal D2 dopamine binding associated with an increase in ligand affinity. PHARMACOL BIOCHEM BEHAV 37(2) 371-373, 1990.--Prenatal exposure to cocaine can result in abnormal neurobehavioral development. This study found an incease in D2 dopamine receptor binding, associated with an increase in ligand affinity, in striatum of weanling rats exposed prenatally to cocaine. There were no changes in D2 receptor binding in nucleus accumbens nor D 1 receptor binding in either striatum or nucleus accumbens. Alterations in D2 dopamine receptors may be associated with neurobehavioral alterations following prenatal cocaine exposure. Cocaine Prenatal D2 receptor Striatum OVER the past decade, there has been a substantial increase in the population of human infants whose mothers have used cocaine during pregnancy (2, 10, 16). Both clinical investigations (3-6) and studies in laboratory animals (14, 24-26) have reported altered behavioral/cognitive function in offspring exposed early in life to cocaine. A number of researchers are beginning to examine the profile of neural alterations resulting from such cocaine exposure. Available evidence suggests that chronic treatment with the dopamine (DA) uptake inhibitor cocaine during ontogeny may result in subsequent alterations in the DA system later in life. For instance, administration of cocaine during the early postnatal period has been reported to increase glucose metabolism and D1 dopamine receptor binding in a number of dopaminergic brain regions, with these effects being dependent upon the sex of the animal and the age of postnatal treatment (8, 9, 23). Gestational cocaine exposure has been reported to alter later psychopharma- cological and neuropharmacological sensitivity to dopaminergic manipulations (26,27), suggesting that alterations in the DA system may also result from in utero cocaine exposure. The present study was designed to examine D1 and D2 dopamine receptor binding characteristics, using the specific ligands [3H]SCH-23390 and [3H]spiroperidol, respectively, in membranes prepared from striatal and nucleus accumbens tissue of weanling offspring exposed gestationally to cocaine. Examination of D1 binding characteristics were conducted in these offspring to determine whether gestational cocaine exposure would result in an increase in D1 binding as has been recently reported for cocaine treatment during the early postnatal period (23). METHOD Gravid Sprague-Dawley rats were placed into one of two treatment groups: one which received subcutaneous (SC) injec- tions of 40 mg/kg/3 cc cocaine hydrochloride daily from gesta- tional days 8-20, and another which received SC injections of 0.9% saline over the same gestation period [see (26) for dosing rationale]. On the day after birth, postnatal day (PND) 1, each litter was culled to 8-10 pups per litter and fostered to an untreated surrogate dam where they were left undisturbed until PND 21. On PND 21, four male pups per litter were sacrificed and their brains rapidly removed and placed on ice. Striatum and nucleus accum- bens were quickly removed by free-hand dissection (13), weighed, 371