Cocaine and lidocaine have additive inhibitory effects on the GABA(A) current of acutely dissociated hippocampal pyramidal neurons

Jiang Hong Ye, Jun Ren, Kresimir Krnjević, Philip L. Liu, Joseph J. McArdle

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Inhibition mediated by γ-aminobutyric acid (GABA) is a major target for the central actions of cocaine and lidocaine, which can result in seizures, especially when these drugs are abused in combination. In the present study, we investigated how cocaine and lidocaine interact to depress GABA current (I(GABA)), recorded by the whole-cell technique in freshly isolated rat hippocampal neurons. Cocaine depressed I(GABA) in a concentration dependent manner, such that cocaine was more potent against lower than higher GABA concentrations: the cocaine IC50 was 0.13, 0.62 and 1.2 mM for GABA at 2, 10 and 100 μM, respectively. Cocaine depressed I(GABA) to the same extent in the absence and presence of 1 μM tetrodotoxin, indicating that cocaine inhibition of I(GABA) is distinct from its Na+ channel blocking action. Lidocaine reversibly depressed I(GABA) evoked by 10 μM GABA with an IC50 of 9.8 mM. In the presence of 3 mM lidocaine, 0.3 mM cocaine depressed I(GABA) (10 μM GABA) to 30 ± 7%. The significantly greater depression by the combined agents (p < 0.05) indicates additive effects on the GABA receptor/channel complex, which are likely to contribute to the additive convulsant effects noted when these drugs are abused in combination.

Original languageEnglish (US)
Pages (from-to)26-32
Number of pages7
JournalBrain research
Volume821
Issue number1
DOIs
StatePublished - Mar 6 1999

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Keywords

  • Freshly isolated neuron
  • Patch clamp
  • Seizure
  • Whole cell GABA(A), current
  • γ-Aminobutyric acid receptor/channel

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