Up-regulation of GABA(B) receptor mRNA and protein in the hippocampus of cocaine- and lidocaine-kindled rats.
To evaluate the effect of GABA(B) receptor in drug-kindled seizures, the gene expression of GABA(B) receptor in cocaine- and lidocaine-kindled rats was examined in this study. Rats were injected (i.p.) daily with cocaine (55 mg/kg) or lidocaine (65 mg/kg) until they experienced a motor seizure (kindling). After kindling, rats received a 1-day, 10-day, or 30-day drug washout period. The rats in the 1-day washout group were killed after the washout. Those in the 10-day and 30-day groups were challenged either with drug or saline, and killed 24 h later. Control rats were injected and challenged with saline. GABA(B)R1a, 1b and R2 mRNAs in discrete regions of brain were detected by in situ hybridization; GABA(B)R1a protein level was measured by Western blotting. Ninety percent of the cocaine-treated rats and 100% of the lidocaine-treated rats were kindled by day 12. Those rats responded to the challenge cocaine or lidocaine with a motor seizure after the 10-day and 30-day washout. GABA(B) receptor mRNA and protein levels in the hippocampus were significantly increased after the 1-day and 10-day washout, but not the 30-day washout. In addition, the levels in drug-treated and drug-challenged rats were significantly greater than those in drug-treated and saline-challenged rats after the 10-day washout. Those data suggest that changes of GABA(B) receptor gene expression could be a factor underlying the development of drug-kindled seizure, but not a necessary component for the maintenance of this phenomenon.
Li
J
J
Department of Cell Biology and Anatomy, Finch University of Health Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Olinger
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AB
Dassow
M S
MS
Abel
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MS
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D003042:Cocaine; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D007696:Kindling, Neurologic / Q000187:drug effects; D008012:Lidocaine; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; D011963:Receptors, GABA-A; D008012:Lidocaine; D003042:Cocaine