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Differential effects of prenatal cocaine exposure on selected subunit mRNAs of the GABA(A) receptor in rabbit anterior cingulate cortex
Journal article   Peer reviewed

Differential effects of prenatal cocaine exposure on selected subunit mRNAs of the GABA(A) receptor in rabbit anterior cingulate cortex

Jed S Shumsky, Yunxing Wu, E Hazel Murphy, Jonathan Nissanov, Ann O'Brien-Jenkins and Dennis R Grayson
Journal of chemical neuroanatomy, v 24(4), pp 243-255
Nov 2002
PMID: 12406500

Abstract

Amino Acid Sequence Rabbits Prenatal Exposure Delayed Effects RNA, Messenger - genetics Molecular Sequence Data Rats Gyrus Cinguli - metabolism Pregnancy Cocaine - pharmacology Gyrus Cinguli - growth & development Animals In Situ Hybridization Time Factors Base Sequence Receptors, GABA-A - genetics Receptors, GABA-A - drug effects Female Gyrus Cinguli - drug effects Receptors, GABA-A - metabolism
We have previously shown that in the dopamine-rich anterior cingulate cortex (ACC), significant changes in gamma-aminobutyric acid (GABA) immunoreactivity occur in the offspring of rabbits given intravenous injections of cocaine (3 mg/kg) twice daily during pregnancy. In the present study, the effects of prenatal cocaine exposure on the developmental expression of specific GABA(A) receptor subunit mRNAs were investigated. We compared the distribution of the alpha1, beta2, and gamma2 subunit mRNAs in cocaine- and saline-treated offspring aged postnatal days 20 and 60 (P20, P60). At P20, prenatal cocaine exposure resulted in a significant increase in alpha1 subunit mRNA in ACC lamina III and a significant reduction in the amounts of the beta2 subunit mRNA in ACC lamina II. No differences between cocaine- and saline-treated controls were detected for gamma2 subunit mRNA levels in ACC. Although the pattern of labeling was altered in cocaine-exposed animals, Nissl sections revealed no differences in lamination, indicating that the changes in GABA(A) subunit mRNAs could not be attributed to abnormal cytoarchitectonics. In P60 brains, no significant differences were observed between cocaine- and saline-treated material, indicating that the observed differences were transient. Collectively, our data show that prenatal cocaine exposure elicits differential, lamina-specific changes in mRNA levels encoding selected subunits of the GABA(A) receptor. Since these changes occur during a critical period when fine tuning of synaptic organization is achieved by processes of selective elimination or stabilization of synapses, we suggest that specific subunit mRNAs of the GABA(A) receptor play a role in cortical development.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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