Prenatal exposure to the dopamine agonist SKF-38393 disrupts the timing ofthe initial response of the suprachiasmatic nucleus to light

The abuse of social drugs Such as cocaine during pregnancy represents enorm ous risks to the offspring. Recent studies showed that drugs administered t o the pregnant rat can activate cell populations in the fetal brain, possib ly altering the timing of key neuronal developmental events. The current st udy examined the ontogeny of light-responsiveness of the neonatal rat supra chiasmatic nucleus using c-FOS protein in SCN nuclei as a marker. The effec t of acute administration of the dopamine D1 agonist, SKF-58393, on the dev elopment of light responsiveness was also examined. Pregnant dams received either SKF-38393 (10 mg/kg) or vehicle 7 after dawn on gestational day 20. Litters were then assigned to one of seven experimental time points from 4 h after subjective dark onset on the day of birth (P0-CT16) at 4-h interval s until CT16 on the day after birth (P1-CT16). Half of the pups in each lit ter were exposed to a 200 lux/2 h Light pulse and the other half remained i n darkness. Three time points (P1-CT0, P1-CT8 and P1-CT16) were used to exa mine the prenatal drug effects on light-responsiveness. Light exposure at t he time of subjective lights on, the day after birth (P1-CT0), resulted in a significant increase in c-FOS-positive cells. The number of positive cell s recorded in the SCN after a Light pulse at P1-CT0 and P1-CT8 was signific antly less in SKF-38393 pretreated pups compared to vehicle treated animals . The exposure to dopaminergic stimulation during gestation may have altere d the timing of development of afferent connections to the fetal SCN, resul ting in alteration of the initial response of the circadian timing system t o light. (C) 2000 Elsevier Science B.V. All rights reserved.