title: Prenatal exposure to the dopamine agonist SKF-38393 disrupts the timing of the initial response of the suprachiasmatic nucleus to light.
abstract: The abuse of social drugs such as cocaine during pregnancy represents enormous risks to the offspring. Recent studies showed that drugs administered to the pregnant rat can activate cell populations in the fetal brain, possibly altering the timing of key neuronal developmental events. The current study examined the ontogeny of light-responsiveness of the neonatal rat suprachiasmatic nucleus using c-FOS protein in SCN nuclei as a marker. The effect of acute administration of the dopamine D1 agonist, SKF-38393, on the development of light responsiveness was also examined. Pregnant dams received either SKF-38393 (10 mg/kg) or vehicle 7 h 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 intervals until CT16 on the day after birth (P1-CT16). Half of the pups in each litter were exposed to a 200 lux/2 h light pulse and the other half remained in darkness. Three time points (P1-CT0, P1-CT8 and P1-CT16) were used to examine the prenatal drug effects on light-responsiveness. Light exposure at the 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 cells recorded in the SCN after a light pulse at P1-CT0 and P1-CT8 was significantly less in SKF-38393 pretreated pups compared to vehicle treated animals. The exposure to dopaminergic stimulation during gestation may have altered the timing of development of afferent connections to the fetal SCN, resulting in alteration of the initial response of the circadian timing system to light.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Adelaide, Medical School, Frome Road, Adelaide, Australia. sferguso@medicine.adelaide.edu.au
authors.forename: S A
authors.initials: SA
authors.lastname: Ferguson
authors.forename: S A
authors.initials: SA
authors.lastname: Rowe
authors.forename: M
authors.initials: M
authors.lastname: Krupa
authors.forename: D J
authors.initials: DJ
authors.lastname: Kennaway
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies; D002940:Circadian Rhythm / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000254:growth & development* / Q000502:physiology
chemical_list: D000906:Antibodies; D018491:Dopamine Agonists; D016760:Proto-Oncogene Proteins c-fos; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine