Prenatal haloperidol alters the expression of DNA polymerases in brain regions of neonate rats.
1. Previous studies have reported a marked reduction in the [3H]thymidine incorporation in forebrain after administration of a dopamine antagonist such as haloperidol. 2. We have investigated the possibility that the expression levels of genes related to DNA metabolism could be altered by haloperidol treatment. 3. By Northern blot analysis, we have studied the steady-state mRNA levels for genes involved in DNA metabolism, in neonate rat mesencephalon and forebrain, after chronic prenatal blockade of dopamine receptors with haloperidol. 4. We found that the expression levels for DNA polymerases alpha and beta were clearly reduced in forebrain by haloperidol treatment. On the contrary, the expression of DNA polymerase beta was increased in mesencephalon. 5. Our results suggest that dopamine receptors occupancy may be a critical factor in controlling cell proliferation during brain development, through a mechanism(s) involving changes in the expression of DNA polymerases.
Castro
R
R
Department of Biochemistry, Georgetown University Medical School, Washington, D.C. 20007.
Brito
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B
Notario
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D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D004259:DNA-Directed DNA Polymerase; D006220:Haloperidol