Endogenous GABA release from rat striatal slices: effects of the GABAB receptor antagonist 2-hydroxy-saclofen.
The reproducibility of endogenous GABA release evoked by multiple periods of electrical field stimulation was examined in rat striatal slices. In these experiments, NO-328 was used to block GABA uptake, and evoked GABA release (overflow) was completely Ca2+ dependent. A seemingly invariant observation in these experiments was that spontaneous GABA release (outflow) progressively decreased as a function of superfusion time and that GABA overflow decreased 25-30% in response to the second of two periods of stimulation (S2/S1 ratios = 0.70 to 0.75). The attenuation of GABA release was not explained by the amount of GABA lost to the superfusion buffer (fractional release), direct depletion of releasable pools of GABA, or slice viability. Furthermore, the decreases in GABA release were not dependent on stimulation frequency (5-15 Hz) or the absolute amount of GABA evoked by electrical stimulation. However, the GABAB receptor antagonist 2-hydroxy-saclofen (2-OH-saclofen; 316 microM) not only enhanced GABA overflow, when superfused throughout both periods of stimulation, but also resulted in S2/S1 ratios of unity. When 2-OH-saclofen was superfused throughout the second stimulation period only, GABA overflow was almost two-fold greater than that evoked by the initial period of stimulation (2-OH-saclofen-free). In addition, these S2 responses were approximately 30% greater than S1 responses that were observed when 2-OH-saclofen was present throughout the entire superfusion period. These results indicate that activation of GABAB receptors was involved in the progressive attenuation of GABA release and further emphasize that GABAB receptors play an important role in modulating endogenous GABA release from striatal slices.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
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Mayfield
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Zahniser
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D002118:Calcium; C057491:2-hydroxysaclofen; D000078308:Tiagabine