Prenatal exposure to cocaine reduces the number and enhances reactivity of A10 dopaminergic neurons to environmental stress.
Prenatal exposure to cocaine has been shown to result in poor cognitive performance in the resulting offspring in humans and laboratory animals. The underlying biochemical changes that contribute to these behavioral effects are not known but have been proposed to involve changes in dopaminergic function. In these studies, we exposed rats to cocaine in utero using the clinically relevant intravenous model and report a mean loss of 24.8% of the tyrosine hydroxylase immunoreactive, presumed dopaminergic, neurons in the A10, but not A9 and A8, cell groups of the young adult offspring. Additionally, in prenatal cocaine-exposed rats dopaminergic neurons in the ventral, midline A10, and lateral A9 regions demonstrated a hyperreactivity to environmental stress, as measured by activation of the immediate-early gene, Fos. Mild, intermittent footshock did not further increase the number of dopamine neurons expressing Fos in prenatal cocaine-exposed rats, as it did in the prenatal saline controls. Because the exposure to cocaine took place during development, other potential changes in dopaminergic and nondopaminergic neuronal systems could result from the cocaine-induced reduction in numbers of A10 dopamine neurons. We hypothesize that a perinatal loss of A10 dopamine neurons, and subsequent developmental changes, contributes to a dysregulation of the adult mesoprefrontal system, resulting in the reported cognitive deficits.
Morrow
B A
BA
Department of Pharmacology, Laboratory of Neuropsychopharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA. bret.morrow@yale.edu
Elsworth
J D
JD
Roth
R H
RH
D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004597:Electroshock; D004781:Environmental Exposure; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D004298:Dopamine