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Endogenous GABA release from rat striatal slices: Effects of the GABA B receptor antagonist 2‐hydroxy‐saclofen
Author(s) -
Mayfield R. Dayne,
Zahniser Nancy R.
Publication year - 1993
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890140104
Subject(s) - stimulation , gabab receptor , gabaa receptor , medicine , endocrinology , chemistry , gaba receptor antagonist , gaba receptor , bicuculline , receptor , biology
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 Ca 2+ 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 GABA B receptor antagonist 2‐hydroxy‐saclofen (2‐OH‐saclofen; 316 μM) 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 ∼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 GABA B receptors was involved in the progressive attenuation of GABA release and further emphasize that GABA B receptors play an important role in modulating endogenous GABA release from striatal slices. © Wiley‐Liss, Inc.