Potentiation of GABAA receptor agonists by GABA uptake inhibitors in the rat ventral midbrain

作者: Ke-Zhong Shen , Steven W Johnson

DOI: 10.1016/S0014-2999(01)01218-3

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摘要: Abstract Whole-cell patch recordings were made from dopamine-containing neurons in the ventral tegmental area (VTA) and substantia nigra zona compacta (SNC). Isoguvacine evoked an outward current (at −60 mV) a concentration-dependent manner with EC 50 of 62±8 μM. The γ-aminobutyric acid (GABA) uptake inhibitor 1-(2(((diphenylmethylene)imino)oxy)ethyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic hydrochloride (NO 711) (3 μM) shifted isoguvacine concentration–response curve to left, new 22±4 l -Arginine mM) also 29±5 increased currents by GABA (100 muscimol (1 208% 261%, respectively. 4,5,6,7,-tetrahydroisoxazolo[4,5- c ]-pyridin-3-ol hydrobromide (THPO) (300 not only mimicked but occluded ability -arginine potentiate isoguvacine. Equimolar replacement Na + choline GABA-evoked currents, suggesting that low concentration has inhibitory effect on transport. Low (25 inhibited still potentiating effects -arginine. We conclude inhibitors actions A receptor agonists, muscimol, probably because they are effective substrates for transporters midbrain.

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