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  • Title: Prolongation of gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO).
    Author: Korn SJ, Dingledine R.
    Journal: Neurosci Lett; 1986 Feb 14; 64(1):47-52. PubMed ID: 3960387.
    Abstract:
    The effects of 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO), an inhibitor of gamma-aminobutyric acid (GABA) uptake, were examined in the rat hippocampal slice and compared to the actions of the potent GABA uptake inhibitor, cis-4-OH-nipecotic acid. THPO reversibly prolonged GABA-mediated inhibitory postsynaptic potentials (IPSPs) but did not prolong conductance changes evoked by iontophoresed GABA. In contrast, cis-4-OH-nipecotic acid prolonged responses to iontophoresed GABA but had little effect on IPSPs. THPO reduced the intensity of spontaneous epileptiform bursts observed in elevated (8.5 mM) potassium; this effect was absent after addition of 100 microM bicuculline. These results suggest that drugs similar to THPO may be useful for enhancing GABA-mediated inhibition, but that THPO acts by a mechanism distinct from that of the GABA uptake inhibitor, cis-4-OH-nipecotic acid.
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