Cocaine decreases the glycine-induced Cl- current of acutely dissociated rat hippocampal neurons

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The effects of cocaine on glycine-induced Cl- current (I(GLY)) of single neurons, freshly isolated from the rat hippocampal CA1 area, were studied with conventional whole-cell recording under voltage-clamp conditions. Cocaine depressed I(GLY) in a concentration-dependent manner, with an IC50 of 0.78 mM. Preincubation with 1 mM cocaine alone had no effect on I(GLY), suggesting that resting glycine channels are insensitive to cocaine. The depression of I(GLY) by cocaine was independent of membrane voltage. Internal cell dialysis with 1 mM cocaine failed to modify I(GLY). Because the depression of I(GLY) was noncompetitive, cocaine may act on the glycine receptor-chloride ionophore complex at a site distinct from that to which glycine binds. The cocaine suppression of I(GLY) was unaffected by 1 μM tetrodotoxin and 1 μM strychnine. Blockers of protein kinase C (Chelerythrine), kinase A (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl, (H-89)) and Ca-calmodulin-dependent kinase (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62)) were also ineffective, which suggests that these phosphorylating mechanisms do not modulate cocaine-induced suppressant action on I(GLY). This extracellular, strychnine-independent depression of I(GLY) may contribute to cocaine-induced seizures.

Original languageEnglish (US)
Pages (from-to)125-130
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Feb 12 1999

All Science Journal Classification (ASJC) codes

  • Pharmacology


  • Cocaine-induced seizure
  • Glycine receptor
  • Phosphorylation-insensitive depression
  • Strychnine-insensitive depression
  • Voltage-insensitive depression
  • Whole-cell recording


Dive into the research topics of 'Cocaine decreases the glycine-induced Cl- current of acutely dissociated rat hippocampal neurons'. Together they form a unique fingerprint.

Cite this