Differential effects of prenatal cocaine exposure on selected subunit mRNAs of the GABA(A) receptor in rabbit anterior cingulate cortex.
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.
Shumsky
Jed S
JS
Department of Neurobiology and Anatomy, MCP Hahnemann University, 2900 Queen Lane, Philadelphia, PA 19129, USA. shumsky@drexel.edu
Wu
Yunxing
Y
Murphy
E Hazel
EH
Nissanov
Jonathan
J
O'Brien-Jenkins
Ann
A
Grayson
Dennis R
DR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics*; D011817:Rabbits; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D003042:Cocaine