title: Regional mRNA expression of GABAergic receptor subunits in brains of C57BL/6J and 129P3/J mice: strain and heroin effects.
abstract: C57BL/6J and 129 substrains of mice are known to differ in their basal levels of anxiety and behavioral response to drugs of abuse. We have previously shown strain differences in heroin-induced conditioned place preference (CPP) between C57BL/6J (C57) and 129P3/J (129) mice, and in the regional expression of several receptor and peptide mRNAs. In this study, we examined the contribution of the GABAergic system in the cortex, nucleus accumbens (NAc), caudate putamen (CPu) and the region containing the substantia nigra and ventral tegmental area (SN/VTA) to heroin reward by measuring mRNA levels of 7 of the most commonly expressed GABA-A receptor subunits, and both GABA-B receptor subunits, in these same mice following saline (control) or heroin administration in a CPP design. Using real-time PCR, we studied the effects of strain and heroin administration on GABA-A α1, α2, α3, β2, and γ2 subunits, which typically constitute synaptic GABA-A receptors, GABA-A α4 and δ subunits, which typically constitute extrasynaptic GABA-A receptors, and GABA-B R1 and R2 subunits. In saline-treated animals, we found an experiment-wise significant strain difference in GABA-Aα2 mRNA expression in the SN/VTA. Point-wise significant strain differences were also observed in GABA-Aα2, GABA-Aα3, and GABA-Aα4 mRNA expression in the NAc, as well as GABA-BR2 mRNA expression in the NAc and CPu, and GABA-BR1 mRNA expression in the cortex. For all differences, 129 mice had higher mRNA expression compared to C57 animals, with the exception of GABA-BR1 mRNA in the cortex where we observed lower levels in 129 mice. Therefore, it may be possible that known behavioral differences between these two strains are, in part, due to differences in their GABAergic systems. While we did not find heroin dose-related changes in mRNA expression levels in C57 mice, we did observe dose-related differences in 129 mice. These results may relate to our earlier behavioral finding that 129 mice are hyporesponsive to the rewarding effects of heroin.
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Schlussman
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: M
authors.initials: M
authors.lastname: Buonora
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Brownstein
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ho
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003627:Data Interpretation, Statistical; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009294:Narcotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D018079:Receptors, GABA / Q000096:biosynthesis*; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000096:biosynthesis / Q000235:genetics; D013045:Species Specificity
chemical_list: D018076:DNA, Complementary; D009294:Narcotics; D012333:RNA, Messenger; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D003932:Heroin
keywords: Brain region mRNA expression; GABA receptor mRNA; Heroin; Strain differences