Details

Autor(en) / Beteiligte

• Campbell, K.
• Kalén, P.
• Lundberg, C.
• Wictorin, K.
• Rosengren, E.
• Björklund, A.

Titel

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

Ist Teil von

• Brain research, 1993-06, Vol.614 (1), p.241-250

Ort / Verlag

London: Elsevier B.V

Erscheinungsjahr

1993

Link zum Volltext

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Intracerebral microdialysis with high pressure liquid chromatography (HPLC) coupled to electrochemical detection was employed to characterize γ-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 μ/min. In the intact CPuu, basal GABA levels were 0.97 pmol/30 μl of dialysate in the awake animals and 0.76 pmol/30 μl 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 excitotoxicity lesioned CPu. Veratridine administered at 75 μM, 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 Mg 2+ added) or tetrodotoxin (TTX, 1 μM) did not alter the basal GABA overflow in the intact CPU under halothane anaesthesia, the omission of Ca 2+ 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 μM 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 μM 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). While glial contributions (as assessed from the excitotoxic lesioned CPu), may account for as much as 20–40% of the basal extracellular GABA levels, more than 95% of the evoked release (i.e. after application of KCl and veratridine) is neuronal in origin. The KCl-evoked GABA release was likely vesicular in nature since removal of Ca 2+ blocked the response by almost 90%. The reductions in basal and evoked extracellular GABA levels seen in the excitotoxically lesioned CPu persisted also after long survival periods, suggesting that functional recovery of GABA release does not occur.