Attenuation of cocaine-induced genomic and functional responses in prenatal cocaine-exposed rabbits.
The effects of in utero cocaine exposure on cocaine-induced genomic and functional responses in postnatal life were examined. Pregnant Dutch Belted rabbits were injected intravenously, twice daily, with cocaine hydrochloride (4 mg/kg) or saline from day 8 through day 29 of pregnancy. Prenatally exposed kits were challenged with cocaine on postnatal day 20. In prenatal saline-exposed kits, cocaine induced time- and dose-dependent c-fos gene expression in both frontal cortex and striatum. Prenatal cocaine exposure reduced cocaine-induced c-fos responses by 35-58% in the frontal cortex and 37-41% in the striatum. Cocaine-induced functional responses that included head bobbing, seizure, and locomotor activity were also attenuated in prenatal cocaine-exposed kits. Cocaine-induced c-fos expression and functional responses were blocked by the D(1) dopamine receptor antagonist, SCH23390, or by the serotonin receptor antagonist, methysergide, but not by the D(2) dopamine receptor antagonist, L-sulpride. The results indicate that in utero cocaine exposure leads to diminished responses to cocaine challenge in the offspring, which may be mediated by prenatal cocaine-induced alterations in one or more components of the D(1) dopamine and/or serotonin receptor signaling systems during early postnatal life.
Tilakaratne
N
N
Laboratory of Molecular Pharmacology, Department of Pharmacology and Physiology, MCP Hahnemann School of Medicine, 245 N 15th Street, Philadelphia, PA 19102, USA.
Cai
G
G
Friedman
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D011817:Rabbits; D012640:Seizures / Q000139:chemically induced; D012702:Serotonin Antagonists / Q000494:pharmacology
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D012702:Serotonin Antagonists; D012313:RNA; D003042:Cocaine