Cocaine selectively alters neurotransmitter receptor mRNAs in mouse embryos.
Alterations in gene expression due to in utero cocaine exposure may adversely affect nervous system development. The present study examined whether or not cocaine administration to pregnant mice alters embryonic mRNA levels for several developmentally-regulated genes. Antisense RNA amplification was performed using RNA from LM/Bc embryos at gestational days 9.5 and 10.5 after three days of cocaine treatment. This technique highlights simultaneous changes that occur in the expression of many genes after a teratogenic insult. Significant changes occurred in the expression pattern on only four genes from a total of 42 candidate cDNAs. These included increases in the relative levels of the alpha and beta 1 subunits of the GABAA receptor without concurrent changes in the non-NMDA glutamate receptor subunits. The results support the hypothesis that in utero cocaine exposure leads to specific changes in gene expression that may ultimately contribute to developmental abnormalities.
Mackler
S A
SA
Division of General Internal Medicine, University of Pennsylvania, Philadelphia, USA.
Bennett
G D
GD
Tsuei
V P
VP
Finnell
R H
RH
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D005865:Gestational Age; D051379:Mice; D009294:Narcotics / Q000633:toxicity*; D011247:Pregnancy; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000235:genetics; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D018076:DNA, Complementary; D009294:Narcotics; D016372:RNA, Antisense; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D018168:Receptors, Retinoic Acid; D003042:Cocaine