Translational issues for prenatal cocaine studies and the role of environment.
Prenatal cocaine exposure produces a wide variety of effects particularly within the nervous system. While not considered a structural teratogen, preclinical studies have documented the biological effects of cocaine exposure during development; effects which to a large extent resemble those described among exposed human populations. This review evaluates the translational value of preclinical studies in terms of three factors: dose of drug administered, timing of events in brain development in the animal compared to human and pharmacokinetics of the drug in animals and humans. Cocaine's effects on cortical development are compared across non-human primate, rabbit and rodent models. Examples of studies utilizing dose-response approaches and clinically relevant plasma drug curves are presented. And lastly, the role of environment in the manifestation of prenatal cocaine effects and published neurochemical effects of enrichment are discussed. The review concludes that there is ample evidence for the biological effects of cocaine on cortical and mesolimbic dopamine system development and that manipulation of the rearing environment can dramatically alter the manifestation of these effects including function of the mesolimbic dopamine reward system.
Dow-Edwards
Diana
D
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Box 29, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. diana.dow-edwards@downstate.edu
D000293:Adolescent; D041923:Adolescent Development; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D038081:Organogenesis / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000523:psychology*; D012931:Social Environment; D013045:Species Specificity
D003042:Cocaine