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Journal article
In Utero Cocaine-Induced Dysfunction of Dopamine D1 Receptor Signaling And Abnormal Differentiation of Cerebral Cortical Neurons
The Journal of neuroscience, v 20(12), pp 4606-4614
15 Jun 2000
PMID: 10844030
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Monoamines modulate neuronal differentiation, and alteration of monoamine neurotransmission during development produces specific changes in neuronal structure, function, and pattern formation. We have previously observed that prenatal exposure to cocaine in a clinically relevant animal model produces increased length of pyramidal neuron dendrites in the anterior cingulate cortex (ACC) postnatally. We now report that cocaine administered intravenously to pregnant rabbits at gestational stages preceding and during cortical histogenesis results in the early onset of hypertrophic dendritic outgrowth in the embryonic ACC. Confocal microscopy of DiI-labeled neurons revealed that the atypical, tortuous dendritic profiles seen postnatally in ACC-cocaine neurons already are apparent
in utero
. No defects in neuronal growth were observed in visual cortex (VC), a region lacking prominent dopamine innervation. In striking correlation with our
in vivo
results,
in vitro
experiments revealed a significant enhancement of spontaneous process outgrowth of ACC neurons isolated from cocaine-exposed fetuses but no changes in neurons derived from visual cortex. The onset of modified growth
in vivo
is paralleled by reduced D
1A
receptor coupling to its G-protein. These data suggest that the dynamic growth of neurons can be regulated by early neurotransmitter signaling in a selective fashion. Prenatal onset of defects in dopamine receptor signaling contributes to abnormal circuit formation and may underlie specific cognitive and behavioral dysfunction.
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Details
- Title
- In Utero Cocaine-Induced Dysfunction of Dopamine D1 Receptor Signaling And Abnormal Differentiation of Cerebral Cortical Neurons
- Creators
- Liesl B. Jones - University of PittsburghGregg D. Stanwood - University of PittsburghBlesilda S. Reinoso - University of Medicine and Dentistry of New JerseyRicardo A. Washington - University of PittsburghHoau-Yan Wang - Drexel UniversityEitan Friedman - Drexel UniversityPat Levitt - University of Pittsburgh
- Publication Details
- The Journal of neuroscience, v 20(12), pp 4606-4614
- Publisher
- Society for Neuroscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000087448500028
- Scopus ID
- 2-s2.0-0034660090
- Other Identifier
- 991019169113204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences