Extracellular gamma-aminobutyric acid levels in the rat caudate-putamen: monitoring the neuronal and glial contribution by intracerebral microdialysis

Brain Res. 1993 Jun 18;614(1-2):241-50. doi: 10.1016/0006-8993(93)91041-p.


Intracerebral microdialysis with high pressure liquid chromatography (HPLC) coupled to electrochemical detection was employed to characterize gamma-aminobutyric acid (GABA) release and the effects induced by a preceding neuron-depleting ibotenic acid (IBO) lesion in the rat caudate-putamen (CPu). Extracellular GABA overflow was monitored in the intact and excitotoxically lesioned CPu, either 7-10 days (acute) or more than 3 months post-lesioning (chronic), using loop type dialysis probes perfused at a rate of 2 microliters/min. In the intact CPuu, basal GABA levels were 0.97 pmol/30 microliters of dialysate in the awake animals and 0.76 pmol/30 microliters under halothane anaesthesia. In both the acute and chronic IBO lesioned CPu the extracellular GABA levels were reduced by 80% and 67%, respectively, under halothane anaesthesia. KCl added to the perfusion fluid at a concentration of 100 mM resulted in dramatic increases in GABA overflow from baseline levels in the intact CPu (60- to 70-fold), which were almost totally abolished (> 95%) in the excitotoxically lesioned CPu. Veratridine administered at 75 microM, produced a 45-fold increase in GABA overflow in the intact CPu, but failed to produce any effect in the lesioned CPu. The addition of nipecotic acid (0.5 mM), a GABA uptake blocker, increased basal extracellular GABA levels 6-15-fold in the intact CPu, while GABA overflow in either the acute or chronic lesioned CPu was not significantly altered. Although Ca(2+)-free conditions (with 20 mM Mg2+ added) or tetrodotoxin (TTX, 1 microM) did not alter the basal GABA overflow in the intact CPU under halothane anaesthesia, the omission of Ca2+ resulted in a 47% reduction in basal extracellular GABA levels in awake, freely moving animals. Nipecotic acid-induced GABA overflow was reduced by 22% under Ca(2+)-free conditions, and by 33% in the presence of 1 microM TTX. Moreover, KCl-evoked GABA overflow was reduced by 86% in Ca(2+)-free conditions and by 40% when administered in the presence of 1 microM TTX. These results indicate that the extracellular GABA levels recorded by intracerebral microdialysis in the CPu are derived predominantly from neuronal sources. Under baseline resting conditions only a small fraction (up to 20-30%) of the neuronal release was Ca(2+)-dependent and TTX-sensitive (i.e. possessing the characteristics of impulse-dependent vesicular release).(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / physiology
  • Caudate Nucleus / cytology
  • Caudate Nucleus / metabolism*
  • Chromatography, High Pressure Liquid
  • Dialysis
  • Electrochemistry
  • Extracellular Space / metabolism
  • Female
  • Ibotenic Acid / pharmacology
  • Neuroglia / metabolism*
  • Neurons / metabolism*
  • Nipecotic Acids / pharmacology
  • Potassium Chloride / pharmacology
  • Proline* / analogs & derivatives*
  • Putamen / cytology
  • Putamen / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tetrodotoxin / pharmacology
  • Veratridine / pharmacology
  • gamma-Aminobutyric Acid / metabolism*


  • Nipecotic Acids
  • nipecotic acid
  • Ibotenic Acid
  • Tetrodotoxin
  • gamma-Aminobutyric Acid
  • Potassium Chloride
  • Veratridine
  • Proline
  • homoproline
  • Calcium