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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
1991-5-23
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pubmed:abstractText |
Perinatal exposure to cocaine has been shown to cause morphological and neurobehavioral abnormalities. In the current study, neonatal rats were given an acute injection of cocaine (30 mg/kg s.c.) at 1, 3, 5, 8, 11 or 15 days of age, and [3H]thymidine incorporation into DNA examined over the ensuing 30 min period. Three brain regions were used that differ in their timetables of cell maturation: cerebellum, cerebral cortex and midbrain + brainstem. Cocaine inhibited DNA synthesis in all brain regions, with diminishing impact as the animals matured; by 15 days of age, the effect of cocaine was no longer significant. Inhibition of macromolecule synthesis was selective for DNA, as [3H]leucine incorporation into protein was much less affected by cocaine. Although inhibition of [3H]thymidine incorporation by a single injection of cocaine was short-lived, repeated administration could have cumulative effects: chronic treatment on days 2, 3 and 4 did not desensitize the adverse effect of a subsequent dose administered on day 5. Additionally, with chronic cocaine, the cerebellum displayed a pronounced rebound elevation of DNA synthesis 24 h after the last dose, a characteristic finding in delayed cell maturation. Inhibition of DNA synthesis by cocaine in developing brain was not secondary to ischemia, nor to local anesthesia, as alpha-adrenergic blockade with phenoxybenzamine afforded no protection, and lidocaine could not substitute for cocaine. In contrast, a small amount (15 micrograms) of cocaine injected directly into the central nervous system readily caused inhibition of DNA synthesis; the same dose given systemically had no effect. These data suggest that cocaine damages the developing brain, in part, through direct interference with DNA synthesis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Lidocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Methoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phenoxybenzamine,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
537
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
197-202
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2085773-Aging,
pubmed-meshheading:2085773-Animals,
pubmed-meshheading:2085773-Brain,
pubmed-meshheading:2085773-Cell Division,
pubmed-meshheading:2085773-Cocaine,
pubmed-meshheading:2085773-DNA,
pubmed-meshheading:2085773-Female,
pubmed-meshheading:2085773-Leucine,
pubmed-meshheading:2085773-Lidocaine,
pubmed-meshheading:2085773-Methoxamine,
pubmed-meshheading:2085773-Nerve Tissue Proteins,
pubmed-meshheading:2085773-Phenoxybenzamine,
pubmed-meshheading:2085773-Pregnancy,
pubmed-meshheading:2085773-Rats,
pubmed-meshheading:2085773-Rats, Inbred Strains,
pubmed-meshheading:2085773-Thymidine
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pubmed:year |
1990
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pubmed:articleTitle |
Cocaine acutely inhibits DNA synthesis in developing rat brain regions: evidence for direct actions.
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pubmed:affiliation |
Department of Pharmacology, Duke University Medical Center, Durham, NC 22710.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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