Up-regulation of GABA(B) receptor mRNA and protein in the hippocampus of cocaine- and lidocaine-kindled rats

Neuroscience. 2003;118(2):451-62. doi: 10.1016/s0306-4522(02)00995-8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Blotting, Western
  • Cocaine
  • Dose-Response Relationship, Drug
  • Hippocampus / anatomy & histology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • In Situ Hybridization
  • Kindling, Neurologic / drug effects
  • Lidocaine
  • Male
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Seizures / chemically induced
  • Seizures / genetics
  • Seizures / metabolism*
  • Time Factors

Substances

  • RNA, Messenger
  • Receptors, GABA-A
  • Lidocaine
  • Cocaine